I've only have 1 (weird) thing cause me to crash. Had 2 of the same sets of clothes, and when I tried to combine them to repair them, or even wear 1 of them, the game would crash. So I just dropped them from my inventory, and game runs fine again. Odd but oh well... I haven't had any problems running it on High, and I have a 285.
And yes, it's the same engine as Fallout 3. Bethesda didn't directly produce this one; a different company did and just changed the textures/storyline/etc. Otherwise, its the same game.