It does not depened on your FPS experience at all because of the Amazing V.A.T.S
It does, and I'm not talking about FPS-twitch skills specifically, but just first-person games generally. This might suprise some of you, but some people really struggle with the whole first-person, dual-stick thing full-stop. For example, my sister-in-law is an avid RPG gamer, but she simply can't play first person games. She just can't (or can't be bothered to) get her head around the controls, how the right stick controls body movement, the left head movement, etc. and so on. She really wanted to play Oblivion, but just couldn't get over this hump. So I would say that, for her, NV would be a fiendishly difficult game.
(I know you can play it in 3rd-person, but come on, to do so is just horrible. Hopefully the new Skyrim engine will rectify that.)