My biggest complaint is that the mouse sensitivity change from the game to the speech interaction is frustrating. It feels super heavy in game and ultra fast in the speech/similar menus.
Could be a problem with the mouse acceleration, the sensitivity was VERY different for me as well in-game/menus, until I added the same command lines for turning mouse acceleration off, just like in Fallout 3.
Add these in Fallout_default.ini (Steam/steamapps/common/fallout new vegas) under the [Controls] section, if you haven't tried it already:
fForegroundMouseAccelBase=0
fForegroundMouseAccelTop=0
fForegroundMouseBase=0
fForegroundMouseMult=0
If that doesn't solve it, try disabling V-Sync in the same INI file by changing "iPresentInterval=1" to "iPresentInterval=0", just like in Fallout 3, the tick box in the launcher for V-Sync does not work.