So after watching over 120 hours of gameplay, I decided to finally buy the game. I thought I would be prepared, knowing how to play, enemy patterns, items, etc. I was wrong. So I started playing, and the first few floors weren't a problem. Up to Caves 2. Or should I say Catacomes. You see, the game really didn't like me apperently. It gave me Basement 1, 2, and then Cave 1, but Catacomes (2), Then Necroplolis 1, and Necropolis (2). Anyways starting from the Catacomes (2) things got really hard. I was always under 5 hearts, and I was about to die. But the Issac god looked down and smiled apon me and blessed me with a pill; full health. Thank the lord. And we went on. I was fine through Necropolis 1 execpt the boss, who was of course the mask and heart. Went into the battle with 3 hearts, left with half of one. The boss droped the 8 Ball, I took it, it gave me the strength card. (Incase you are unaware, the Strength card gives you all stats up[Health is a stat] for a room, and a heart) Made my way into the the Necropolis (2), first room, I popped the strength card and my book of shadows, so I wouldnt take any damage on the room and still keep a heart. Yadada explored the full floor, made it to the boss. I was thinking, how in the damn world was I going to beat Mom with 3 hearts and with my book of shadows on cooldown? {So the important thing to know here is I was not underpowered. I had a very lucky run, itemwise. The most important things I had were; Quad Shot, Poison Touch, Book of Shadows, and 8 Heart containers}. So I went into the Mom boss fight with 3 hearts, and, holy crap, I did it with half a heart remaining. That was one of the happiest moments (and most suspenceful) of my life.

So what was your best run?

I remember getting nearly max damage, sacred heart (homing shots HUGE TEARS), flying, book of revelations. Easy as pie

@Sayishere: Dear god. Sacred tears don't appear as often as they used to. That sounds amazing. Did you get any of the batteries with book of revalations? I find book of revalations is only slightly useful unless you get it early game or with some method to recharge it. If you were to get the wafer, the nun's habit, and then book of revelations you would be immortal.

My best run involved going to a secret room outside of the dungeon with teleport, x-ray glasses, the physician powerup (for better pills) and a lot of great pills, among two full health ones. That's how I beat the last boss for the first time.

Last night! I only had Satan left to beat and I got a ton of amazing upgrades Third eye, rage, rock, little chad, rainbow baby, coal, attack fly, always alone, various health, blessed and a couple of other things... had Mom's pearl all the way up to the final room and then a slot machine dropped the tick. Beat Satan easily.

I've played that game for 7 hours and have yet to come close to beating it. Unless that skull on the map screen is the last boss then I got to the floor right before it once.

@Omega: If you mean on floor 6 [KIND-OF-SPOLIER], more bosses are to come..... dun dun dun

[REAL SPOILER (DONT READ IF YOU DON'T WANT SPOILED MILK {if you dont want for me to spoil the game })] After you beat mom, the boss of the 6th floor, you unlock more floor, with 4 more "final?" bosses (Mom's heart, Satan, Issac, Blue Baby)

On my Dark Boy run - I ended up with a heap of tears up items/pills until I ended up with the maximum rate of fire; then I got the cancer trinket, which gave me double the maximum rate of fire; then I got cupid's arrow; so, I basically ended up with penetrating machine gun tears :o

Not exactly my best run, but I slaughtered the shit out of the Necropolis :o

OMG on a slightly unrelated topic, I'm shaking due to the most amazing thing. After that amazing first run I wrote about, I died one time. On my third run I got polyphemus a shit ton of damage and max fire rate for polyphemus... and I beat Mom's heart on my 3rd game. Holy crap. I... am literally trembling it was fucking amazing. 99 min says on steam, Unlocked 19 secrets, Maggy, Judas, and Samson, and beat Mom's heart. omg.

By the end of one run in Wrath of the Lamb, I got Brimstone, a cube of meat,the Common Cold, the Compass, the Relic, some flying item, Book of Belial, and two followers. I was unstoppable. Now I can't even get a damage up as Eve. I hate Eve.

When I played Maggie, who has Yum Heart (which gives you a full heart when it's charged), and got "Habit", the nun outfit that fills half your charge everytime you get hit. It pretty much means unlimited life and yeah, that helped. 
 
May I ask why you watched 120h of gameplay?

I had ipecac to thank for my first run that beat Mom's first form. Just beat Mom's heart by doing the Dr. Fetus challenge, which felt a little cheap, but it was interesting to see this whole world of new enemies and bosses even if unlimited bombs were my tour guide. 138 deaths, 1 mom kill.

Really? 120 hrs of gameplay? I'm well versed in the art of time wasting, but that is just on a whole other level.

@Lobster_Ear: Yeah, I had to read that a few times to let it sink in. I can't imagine just watching a game for that long, and then still being interested in playing it.

On topic, I've never even come close to having a "run" in this game. I always play through a few levels and end up dead.

One of my first runs after buying Wrath I got Nail, Habit and just a ridicolous fire rate on cain. It was like literally a stream of tears and habit + health regen items is just utterly broken, especially nail with a ton of coins and arcades. Got ipecac, habit + yum heart (played maggy) just a few runs later and just ruined my way to Isaac again. Haven't had any similar luck since then =(

@Lobster_Ear said:

Really? 120 hrs of gameplay? I'm well versed in the art of time wasting, but that is just on a whole other level.

My thoughts, too.

I got 25 hours logged into this game and I've had plenty of great moments. But all this thread made me realize is that I haven't played since i bought Wrath. Time to change that!

@Lobster_Ear I watched every single episode of Northernlion's BoI lets play, over 200 episodes, aside from a few other youtubers. Since I knew everything about the game I felt compelled to buy it. It was worth it.

Also, the reason I didn't get bored of the game is because, well, the game is NEVER the same! The replay value is immense and your never paired up with the same thing twice. Its like having a 200 sided die, and rolling it 300 times, and seeing if you get the same numbers in the same order. The moment I have two exactly the same Issac runs, I will give an equivelent of all the money I spent on steam to a random person on the street. Or a bum. They could use the money.

I was playing as eve and the first treasure room i got dr. fetus and for the first boss i got headless horseman.

Dr. fetus + flight = Win. Easily made my way to the chest and dominated

Probably not my "best" run but considering i was playing as eve and the odds are kind of stacked against me in that sense, it was sweet

I also watch Northernlion's Binding of Isaac lets play. I usually play while listening to him play, makes me feel like we're in a competion. I got Wrath of the Lamb during the Steam Summer Sale, and by that point he already knew all the enemy patterns and what every item does. I'm a bit behind on videos still. I just have to beat the Cathredral boss with Eve. Then I can worry about beating the Chest with all the other characters. After that I just have to find all the items to get Platinum God. This will be the 1st game I get S Rank.

I just played a game with Habit + Mom's pill bottle while playing Cain. For those that don't know habit is an item that gives you half of your charge on your item when you get hit and mom's pill bottle spawns a random pill, also Cain can only have good pills. the emd result was max tears and max range with pretty sick damage as well. To make things funner I bought the flying + spectral tears item from the devil room and later in the run I switched out mom's pill bottle for book of revelations to ensure invincibility. unfortunately I never got lump of coal, which would have been sick.

My best run was with Cain and finding the dollar from the slot machine in the first secret room. From there I had gotten brimstone, super meat boy, the steam sale, little steve, the skeleton key which were converted into bombs, then the homing bombs, a 1up, multiple blood bags for max health, x-ray glasses, and all the recharge items. I was also able to get the dead bird and had the book of shadows as my item. By the end of my run, I was also maxed out in every stat. It was the luckiest run I ever had, I took barely any damage past facing Mom.

Getting the dollar and then the skeleton key ensured that I was pretty much set as I could buy almost anything. Being Cain and having the lucky foot also ensured that I could stay in the arcade room and get lucky with getting blood bags and extra money.

Book of Shadows + Poison Touch + Battery

I beat the full game up through Sheol in like 25 minutes.

I also just had a poison touch + book of shadows run. i also gave all my hearts to the devil so I also got a 5 second shield each time i got hit because of the polaroid. Beat blue baby in no time.

I still haven't even beaten Mom, so not very good runs so far in around 5 hours of game play.

Just picked up the game a couple nights ago, finally beat Mom today after about 7 total hours of playing. Had a pretty good run, didn't find many spacebar items (was stuck with Shoop da Whoop for most of the game), but found some pretty decent stuff - got the triple-shot early on, a couple damage upgrades, tons of bombs, a couple blood packs, a dollar....made things pretty easy, but I doubt I'll be making it that far again very soon.