This thread comes a bit late but I've clocked 36 hours now and figure I should start a thread before the Humble Bundle with the game ends.
The Binding of Isaac was designed by Edmund McMillen, you may know him from Super Meat Boy, Time Fcuk and Gish. It's strongly based on the first Legend of Zelda but takes a different approach to the formula: It's kinda like a roguelike. Well, in structure. It's random generated, you dive into a dungeon to beat the boss at the end and if you die you lose the game and have to start over. Unlike real roguelikes it's an action-based game and a run doesn't take more than an hour (often much less, depending on how long you survive).
Like Super Meat Boy it's both hard and gross: You'll take dozens of tries to beat the game even once and then it just unlocks more crazy stuff so you'll want to replay it right away. But you're also a little boy caught in his nightmare world, just before his mother will kill him. Naked and unarmed. Your only weapon are the tears you cry which can kill the various monstrosities (which are often clearly ex-human) of the dungeons. Blood and feces are everywhere. Urine is a weapon too. Upgrade items turn you more and more into a mutant or a demon. Yet, like Meat Boy, it's drawn in a cute way that makes the nightmare world not as horrible as it may sound.
The game is also hilarious, with tons of videogame and pop culture references among its over 100 items.