Probably the funniest and most entertaining thing you can do in BOI is break the game.
And no, not with overpowered items, I mean literally breaking the game.
https://www.youtube.com/watch?v=Vix9sr9w490I did this about four days ago and I lost most of the recording(due to not having camtasia installed). I had completely fried the game.
For those who do play the game, if you have the items that come in the expansion The Wrath of the Lamb, more specifically the Habbit and the Scapular, you can use those two items in conjunction with the item the D6(unlockable to start the game with), to spawn in the D20(assuming you have it unlocked as well).
Now if you use the D20 with the Habbit and Scapular you can do what I did, although I went WAY overboard to the point where my computer almost crashed. You can use the D20 in this combo to spawn an infinite amount of dropables and chests which can contain items. And then you can switch to the D6 an=ter enough item spawning to reroll the items into better ones.
The downside(or upside because crashing=winning) is that rerolling tends to empty the item pool because items dont come back. So eventually the game will run out of items to give you and at that point it just crashes. In a hilariously funny way though.