What happens when one half of a development team goes on holiday and leaves the other, slightly agoraphobic half at home? In a roundabout way, it ends up in The Binding Of Isaac. That's the origin of the game, the very moment that sent Edmund McMillen down into the basement to confront elements of his religious upbringing in a Flash game. Isaac's odd story is told in this interview from the makers of Indie Game: The Movie. Want to hear about how Ed's Team Meat partner Tommy Refenes' holiday turned into a game of contradictions? It's posted below, and it's absolutely fascinating.
EDIT: The video was live when I wrote the story, and now it's private. WHAAAAAAAAAAAAAAAAAA!
None of Isaac makes sense. It's ugly, but inspires fan art. He's not happy with the technical details, the art, or the fact that he made it in Flash, but it's because it's been built in that engine that so many people have been able to play it and turn out Let's Plays, which helped sell the game. McMillen's belief in difficult art means he set out to to make a game that he hoped might damage his career, but it ended up selling over a million copies.
And then there's the theme. The poke into the religious upbringing, both the positives and negatives that came with it. Rather than summarising it, I'll let Ed speak his mind on that, because I'd hate to have a quote come across wrongly on the page.