Perhaps the ending has a bit to do with it, but I saw this as much more in the Barton Fink vein of the Coens' oeuvre. I don't see it as nihilistic at all.
In A Serious Man, the combination of slapstick and ironic distance, sometimes called the Coens' disdain for their characters, works in large part because in a certain way, Larry is superior, or thinks he is, to the characters around him
Spoiler
until the end. Moreover, his "superiority" only serves to confuse him and accelerate his downfall; when he goes up to the roof to fix the antennae, he surveys his neighborhood from a heightened vantage point, but winds peeping on his neighbor, with whom he'll later have sex.
In a different sense, of course, he's entirely too passive and he clearly missed the opportunity to put his foot down in his own house. But I'm just talking in terms of Larry's attempt to understand his misfortune and do the right thing while everything around him goes wrong.
And I thought the ending was phenomenal (again, a la Barton Fink). But I don't have anything to add on that score b/c Grand Illusion and Cronenfly's posts seem pretty spot-on to me.
