The inclusion of skill magazines, just really don't like the very *idea* of being able to raise skills temporarily in such a manner (20 freaking points with the right perk). At least raising stats with drugs can have a downside (though too slight). So yeah, bleh for skill mags.
Given that skill books are rarer, I -- and my current low-INT character in particular -- am very grateful for the magazines. Though they should maybe be more expensive.
Most of the really annoying flaws that come to mind are bugs -- unlistenable radio and crazy arms being the two most persistently annoying -- but the screwed-up karma annoys me. Also, a fair few of the game's quests feel incredibly fragile and easy to break, this is not one of those games where you think "http://tvtropes.org/pmwiki/pmwiki.php/Main/TheDevTeamThinksOfEverything".
And I wish that travelling was slighlty less sedate, that there was more traffic on the roads, random encounters, even just being jumped by raiders more often.
Oh, and: I find the second act of the main quest to be quite awkwardly-paced, with the player having a load of end-game junk dumped in their in-tray almost as soon as they hit the Strip, quite possibly well before they've thought much beyond life after Benny.