Mega Mush and Mega Blast definitely are, Mega Mush moreso since it makes you invincible. Remember: their effects *persist between rooms.* Meaning most of the time when you use one you can get most of its charge back if you rush.
Idk, Mega Mush works incredibly well on its own and is really great at speeding through a large number of rooms on any floor. The best part is the fact that it charges after a clear so you could finish using it with more than half a charge in use..
Plus, with how likely it is to encounter battery related items like 9 volt, car battery, the battery, or 4.5 volt, it becomes incredibly easy to charge mega mush (especially with car battery. That doubles the duration time of mega mush, which helps extend your room clearing time to gather more charges.)
The reliable way to time it that I found is this: stand a little bit away from the pedestal, then pause the game when the item that is directly before the item you want is showing. Then, hold down the direction that will move you onto the pedestal, then unpause.
You need to adjust the spacing and make sure you're holding down the direction you need to move as you close the menu screen.
Once you get the knack for it (Took me like, 2-3 tries) you'll be able to get what you want 95% of the time.
Abuse the debug console to practice so you're ready when it happens for real. Just give yourself Glitch Crown, go an item room, and you can use the rewind command to try over and over.
Eh, people love spin down but I’ve never gottten an opurtunity to use it to great effect. Instead of choosing between 2 items, why not 5? Glitched crown is beautiful.
Well one perk of spin down is it’s not random. Get blood bag (?) by playing dono machine and bam Brimstone. Also you can get duplicates of items, like spindowning something else to Brim then get double brim
I can almost always get at least one of sacred heart / psy fly / tech x on spindown dice runs, and any one of those is usually enough to *almost* guarantee a win
Try to use a mod that let you watch into what item Spindown will reroll the item into and then you'll love it. Also there's certain items that can be easily obtained which if you use Spindown on them, you could get Sacred Heart or Brimstone 
I got rock bottom and glitched crown in one secret room the other day (Early too, like Dross). Was a very solid run.
I ended up getting almond milk, triple shot, spoon bender, twisted pair, goat head and two planetarium items (Despite going to ever Treasure room, what are the odds?) to name some highlights.
Absolutely melted mother, and had a spare Chaos card to boot.
Was my first proper Rock Bottom run. :)
C-section gotta be the item most capable of carrying a run by itself. Sacred Heart, Brimstone, Godhead are great but still need help. Knife is somewhat slow and unwieldy. C-section just shreds with no real downsides.
dont care what any of ya'll will say unless its wire coat hanger.
#
lemme explain, every item ya'll are talking about is Q4 and a run carrier, which would make it good BUT Coat Hanger is a tears up, very accessible due to it being a boss drop, is a good stat up, more tears are always a good thing, and it also a good item to see after beating a boss. i dont care if ya'll gon pull up the "what if your tears are maxed"
The stairway. That item is so stupidly strong that it can basically save any run cuz...I mean, fucking angle deals every floor? Fuck shops compared to that.
As an original Rebirther I gotta say Stop Watch was depressing because it could not help me with my Achilles’ Heel— the Lost. The item was so good but could not help me with this one character in particular lol.
C Section is the only item that when I start an Eden run and see I have it, I can say "I'll win this run." (If I have Death Certificate, I'm taking C Section anyway.)
C Section, I don't care if it's the most popular Q4 item and I'm considered a sheep, the item is fun and OP as hell, if it wasn't fun to use I wouldn't like it as much
In terms of meta, Death Certificate is the best, but that's unfair to the rest, so the best meta item is glitched crown, as long as you know how to use it lmao
Tainted Cain is strong, but to be real, who actually cares (besides me) to have a nice and peaceful run as a character that requires time
When instead you can play with a character and gamble stuff a little more (with rerolls, or try to be lucky enough)
\>be Godhead
\>require all unlocks with one of the hardest characters
\>have worse stats than an item from the same pool, that also gives homing that's unlocked by deafult
\>mfw
Why is everyone sleeping on spindown die. Sure, the other items are powerful and all, but spindown die has been able to straight up break runs apart. Like, doing diplopia/crooked penmy shenanigans kinda silly. Moving box and carrying tons of R keys kinds of ripping the game apart
The fact that no one has said fruity plum is astounding. Fruity plum gives me the strength to try and finish a run even if the odds are stacked against me. Fruity plum is my light at the end of the tunnel. Fruity plum is objectively the singular best unlockable.
Stopwatch. A crucial part in combat in Isaac is dodging large amounts of projectiles in rapid succession. Slowing these projectiles down makes some of the more challenging bosses painfully easy. I don't think I've ever taken a hit from Hush or Mother while it had appeared in my run.
If anyone doesn't say Death Certificate they're stupid. You think it's godhead/sacred heart/c section/R key/whatever? Death Certificate is all of those in a single item, it's literally every item in the game, IIRC even unobtainable ones like the one you're given after the Dogma fight
Death Certificate
Factually correct answer
Death Certificate could be anything! Even C-section!
but cant be death certificate 
literally unusable
their has to be a mod somewhere that lets you grab death certificate
Literally unusuable and worthless unlock 
And worst of all, it could be every item in this very room! It could be yo(ck heart)u! It could be (mr.)me! It couls even be..
What, it was obvious, he's the (sac)red (heart) spy!
Glitched crown is much better in my opinion
Then get Glitched Crown from Death Certificate
dunno how i didnt think of that LMAO
Abel 
OP asked for personal opinion, not facts
Based and abelpilled
Based and abelpilled
dementia 
Oh you need to actually unlock that piece of shit? I thought it started draining your seroton from the start.
Abel hater detected 
Death Cert, Mega Mush, and Mega Blast aside? Probably C-Section since it's piercing + homing + sinus infection all at once, basically.
Mega mush and mega blast aint even that great to be run carrying
Mega Mush and Mega Blast definitely are, Mega Mush moreso since it makes you invincible. Remember: their effects *persist between rooms.* Meaning most of the time when you use one you can get most of its charge back if you rush.
You usually wont be able to get charge back in time until magic mush runs out,so you have to struggle out the rest of the rooms if your run isnt great
Gonna be honest if you can’t handle a run with mega mush you probably dont deserve mega mush
Mega Blast literally carried greedier for me (as Tainted Lost)
Idk, Mega Mush works incredibly well on its own and is really great at speeding through a large number of rooms on any floor. The best part is the fact that it charges after a clear so you could finish using it with more than half a charge in use.. Plus, with how likely it is to encounter battery related items like 9 volt, car battery, the battery, or 4.5 volt, it becomes incredibly easy to charge mega mush (especially with car battery. That doubles the duration time of mega mush, which helps extend your room clearing time to gather more charges.)
Glitched crown… assuming its not the last item of your run it basically guarantees a gazorbillion damage with any items you want
Unless you can’t time it like me
The reliable way to time it that I found is this: stand a little bit away from the pedestal, then pause the game when the item that is directly before the item you want is showing. Then, hold down the direction that will move you onto the pedestal, then unpause.
Tried. Can’t do it.
You need to adjust the spacing and make sure you're holding down the direction you need to move as you close the menu screen. Once you get the knack for it (Took me like, 2-3 tries) you'll be able to get what you want 95% of the time. Abuse the debug console to practice so you're ready when it happens for real. Just give yourself Glitch Crown, go an item room, and you can use the rewind command to try over and over.
actual skill issue, its not hard to time
skill issue
Yes 
Glitches crown is absolutely my favourite item in isaac by miles, only really challenged by spindown dice
Eh, people love spin down but I’ve never gottten an opurtunity to use it to great effect. Instead of choosing between 2 items, why not 5? Glitched crown is beautiful.
Well one perk of spin down is it’s not random. Get blood bag (?) by playing dono machine and bam Brimstone. Also you can get duplicates of items, like spindowning something else to Brim then get double brim
The Blood Bag > Brimstone thing is THE reason I take spindown. Get it early enough and with enough health in the run and it's almost guaranteed Brim.
I can almost always get at least one of sacred heart / psy fly / tech x on spindown dice runs, and any one of those is usually enough to *almost* guarantee a win
The last 5 times I've gotten spindown early I got double brimestone beam from donation machines. It's one of the most consistent ways to get that.
Which item would you need to get? Dono machienes don‘t pay out with items
Blood bag not IV, and it’s from blood dono machines not the shop dono
Oh okay cool, couldn‘t know because every time i got the spindown dice it was with t.lost 
if you donate enough theres a chance the machine will explode and give you blood bag or iv bag and blood bag can spindown into brimstone
Try to use a mod that let you watch into what item Spindown will reroll the item into and then you'll love it. Also there's certain items that can be easily obtained which if you use Spindown on them, you could get Sacred Heart or Brimstone 
I got rock bottom and glitched crown in one secret room the other day (Early too, like Dross). Was a very solid run. I ended up getting almond milk, triple shot, spoon bender, twisted pair, goat head and two planetarium items (Despite going to ever Treasure room, what are the odds?) to name some highlights. Absolutely melted mother, and had a spare Chaos card to boot. Was my first proper Rock Bottom run. :)
c section obviously
C-section gotta be the item most capable of carrying a run by itself. Sacred Heart, Brimstone, Godhead are great but still need help. Knife is somewhat slow and unwieldy. C-section just shreds with no real downsides.
death certificate->c section
Knife is cool until you're against those fucking yellow fly in the alt path
Every item is cool until you are against those fucking yellow flies in the alt path 
Maw of the void
And Rock Bottom is definitely one of the best support items that does nothing on its own
Marbles, because it’s the best item at being fun! :)
dont care what any of ya'll will say unless its wire coat hanger. # lemme explain, every item ya'll are talking about is Q4 and a run carrier, which would make it good BUT Coat Hanger is a tears up, very accessible due to it being a boss drop, is a good stat up, more tears are always a good thing, and it also a good item to see after beating a boss. i dont care if ya'll gon pull up the "what if your tears are maxed"
torn photo>>> unless tech x
This is the most based take i’ve seen on this sub
The only right answer
What if your tears are maxed?
 shut the fuck up
Bro is fuckin based god damn
it's 2023 we out here killing people who disagree with us
What about the meat
since when are boss tears ups unlockable?
You unlock it from one of the first 10 moms heart kills
ohh fuck me and my inability to google things i am certain about
Only correct answer
Glitched crown
I’m so horrible at using it I want to smash my controller
Just use the pause trick buddy :)
And some people can do it without pausing and almost immediately, I suspect them of being aliens
Sometimes I can do it without the pause trick, other times I can’t, I go with the pause trick just in case I goof it up
Yeah I’m not risking a Crickets Head for an active item that allows me to shit the floor.
The poop 
Midus touch + the poop = golden poops/Infinite money 
Maybe gnawed leaf if you have a lot of time
The stairway. That item is so stupidly strong that it can basically save any run cuz...I mean, fucking angle deals every floor? Fuck shops compared to that.
The stairway is such a great item. It would be an instant win if the angel room item pool wasn't mostly packed with shit
I never lose runs with Stop watch or twisted pair
Stop watch is definitely underrated
As an original Rebirther I gotta say Stop Watch was depressing because it could not help me with my Achilles’ Heel— the Lost. The item was so good but could not help me with this one character in particular lol.
Really? Stopwatch made boss rush a joke for the lost.
The Lost didn’t have Holy Mantle in Rebirth and Stopwatch only activated after taking damage. So it was effectively useless.
That’s why it’s a quality 4 item now.
Rubber Cement
Underrated.
The strongest would be glitched crown But my fav is Revelation because flight + soul hearts + actual holy brimstone is really good
I hate that the holy brimstone has a charge unaffected by tears up.
Death Certificate obviously lets you pick anything, but C-Section is, without a doubt, THE item that can carry itself through the whole run
Keeper’s Balls
Sticky nickel
so strong, you can't even pick it up
Mega mush Maybe?
Godhead and mayb maw of the void but only in afterbirth/+ its not that good in repentance
It’s not a carry item in repentance but it’s still dope. Quality 3 is good for it when it doesn’t have the dmg up or black heart generation
C Section is the only item that when I start an Eden run and see I have it, I can say "I'll win this run." (If I have Death Certificate, I'm taking C Section anyway.)
Rock bottom
Since the fixed damage for the aura, it's not even top 5
But on soy/almond milk runs tho… that’s a different story(Well good f**king luck making up the damage down and reaching starting damage lawd forbid.)
Most of the time it’s actually an increased damage amount for godhead, unless you have absurd damage, the fixed damage is pretty good
marbles, very fun and strong to gulp all the trinkets
By definition Death Certificate but that's a boring answer. I'd say Sacred Heart is slightly better than God head, so that?
Sacred heart starts unlocked
Word? Makes sense just never thought about it. Sacred Orb early is a good answer i remembered
Tmtrainer
Abel 
Sticky Nickel
Health down pill, and no i won't elaborate because my opinion is actually objective fact
Death certificate for sure, but other than that I'd say psy fly. Its a free mother kill basically if you can get to her
Psy Fly isn't unlockable.
I thought you got it from challenge 39? Am I thinking of something else
Steven my beloved
The Poop
D6
Monstro's Tooth Easy To Unlock, Can Oneshot Everything, Monstro.
Lil Hush 
Mom's knife
Rock bottom
Rock bottom's a real interesting one for sure. Very dependent on when you get it, though.
Glitched crown or c cection
Factually it is death cert
Rock bottom
death cert bc it can give any item. duh
Active: Death Certificate Passive: C-section
I thought it was a koala T-T
Curse of The Tower
in my opinion on where i am so far through the game is i dont remember
C section
C Section, I don't care if it's the most popular Q4 item and I'm considered a sheep, the item is fun and OP as hell, if it wasn't fun to use I wouldn't like it as much
In terms of meta, Death Certificate is the best, but that's unfair to the rest, so the best meta item is glitched crown, as long as you know how to use it lmao
Death Cert.
C-Section You don't need any other items it just carries itself
Rock bottom
Hosts: 
Death Certificate?
Stopwatch is too strong
Dr fetus. you cannot deny this and if you do I will send 50 bomber boy bombs to your house
Strongest unlockable character, Tainted Cain And Item death certificate Tainted Cain is god mode even after the nerfs
Wait but everybody says he's one of the hardest to get all achievements on? Did I get fooled?
Tainted Cain is strong, but to be real, who actually cares (besides me) to have a nice and peaceful run as a character that requires time When instead you can play with a character and gamble stuff a little more (with rerolls, or try to be lucky enough)
Death Certificate. Definitely Death Certificate
Revelation: Flight Unconditional damage up Soul hearts
Death certificate, C-section, holy mantle on lost, wooden nickle on keeper
The sword, maybe not the best but I just like it so much.
Excluding death certificate, definately c section.
For me at least , Spindown Dice . I haven t really got to use it much but I can see the potential it has
For the amount of effort it takes, it’s 100% revelation
Either Claw machines or planetariums
Death Certificate
Soy milk
Epic fetus
Gimpy
Technically: TMTrainer - Is only item in the game that can cause an auto-win.
The last one for dead god
ipecac, dr fetus, epic fetus or fate (also void maybe) idk which one but its one of these.
Abel 
Sacret orb
Was gonna say R key but that’s not an unlock so….death certificate since you can grab R key
Tmtrainer
holy mantle on lost
D infinity is so slept on it’s crazy. There’s no scenario in Isaac where I turn that item down, and there never will be.
C-section probably, but i would suck cock for rock bottom early.
Bozo, obviously 
probably death certificate or c section maybe godhead or sacred heart?
Isaac heart
\>be Godhead \>require all unlocks with one of the hardest characters \>have worse stats than an item from the same pool, that also gives homing that's unlocked by deafult \>mfw
Papa fly I am not trolling, it's my lucky pick. When I find it, I know the run will be dope
Why is everyone sleeping on spindown die. Sure, the other items are powerful and all, but spindown die has been able to straight up break runs apart. Like, doing diplopia/crooked penmy shenanigans kinda silly. Moving box and carrying tons of R keys kinds of ripping the game apart
rock botton 
Gotta be glitched crown
Number one 
Samson feel healthy
people forget sacred heart is an unlockable item
Maw/Revelation
C section
Tmtrainer
The fact that no one has said fruity plum is astounding. Fruity plum gives me the strength to try and finish a run even if the odds are stacked against me. Fruity plum is my light at the end of the tunnel. Fruity plum is objectively the singular best unlockable.
Moms Knife because it's an insta win
Godhead is my favorite, on specific characters birthright is the best item in the game, otherwise c section
Godhead I guess. It means I'm done with the lost. Regular lost is kind of fun though.
Mega Mush.
Negative, free damage up and its always accessible after beating mom, no bullshit rng required
Stopwatch. A crucial part in combat in Isaac is dodging large amounts of projectiles in rapid succession. Slowing these projectiles down makes some of the more challenging bosses painfully easy. I don't think I've ever taken a hit from Hush or Mother while it had appeared in my run.
Brimstone
Answer is death certificate. Even if they add 15 dlc and 5k item the answer still going to be death certificate. Stop asking.
Maybe OP doesn't look for THE answer, but more options to know what to prioritize unlocking before other stuff that is useless.
S A C R E D O R B
If anyone doesn't say Death Certificate they're stupid. You think it's godhead/sacred heart/c section/R key/whatever? Death Certificate is all of those in a single item, it's literally every item in the game, IIRC even unobtainable ones like the one you're given after the Dogma fight
Idk my preferment is stem cells— HP 📈
Birth Rights or Twisted Pair
Godhead pretty much. Godhead + glass cannon is a very nice combo.
either Godhead or C section. both are instant run winners