I really only have a few major issues:
1. Armor and weapons cost a sh*tload to repair, like over 10k caps for some medium end weapons and armor (not talking about the power armor). I really don't want to have to resort to 'farming' caps from numerous runs on Black Mountain or what-have-you.
2. Armor seems to break from a swift breeze, then refer to #1.
3. Melee mobs tend to run/jump at mach speed and the proceed to gang [censored] you while you desperately try to back-peddle. Then refer to #1.
Other than that, I wubs it=)
Addendum:
Some minor issues:
1. I told Rex the cyberdog to wait for me in town while I went to clear out vault 11? (the one with the plants) and as I was using the elevator he mysteriously appear beside me, still waiting, but then appeared on every floor I went to.
2. Game really needs to be graphically optimized. Frame rate actually drops on my gtx480 in a few places ( New Vegas for one). The gfx tech is 2 years old so there really is no reason it should slow down. Seem to happen primarily with a lot of NPCs in view.