I have the biggest shits right now with Fallout 3.
I picked up my copy and installed it....and then no matter what I did, it wouldn't run. I tried all the possible solutions, including the official patch, ini file mod, etc etc
last resort............grab my other HD and shove it in the computer, do a fresh install of Vista without all the other crap and see if it runns...........if it doesn't, I'm gonna trade it in for a PS3 copy