Wow. What an amazing film, one of the Coen Brothers best, and that is saying a lot. Apparently this grew out of an idea for a scene involved a stoned kid at his bar mitzvah (which is in the movie, and is very, very funny) and just grew from there into a meditation on suffering.
This film is deeply concerned with religion, and one of the themes that I think it drives home very well is that religious explanations for suffering are seriously lacking. The film can be seen as a modern re-telling of the Book of Job.
My review is here: http://alenthony.wordpress.com/
No spoilers in it, though I do discuss what I think the film is trying to say - this would be a very hard film to "spoil" - knowing what happens at the end would not really impact it. I don't think of it as a plot driven film.