Depends on what you like. There are very few games I have ever replayed, because once the game mechanic has worn out, and all the surprises have been seen, that's pretty much all there is to it. I can watch good movies over and over again, because the quality of the writing, acting and directing is unquestionably superior. I've also re-read more books than I've replayed games. Uncharted 2 was a fantastic game, but once was pretty much all I could handle. I can't think of a game I played through more than one time this generation that didn't have full campaign co-op and an extreme difficulty setting. That list is almost nill. It isn't a knock against Uncharted. It's the nature of the beast, but it's a reasonably consideration to think about how much play you'll get out of a game before you buy it.
I remember completing Halo 2 four times when I purchased it -bundled with the original Xbox- during Christmas 2004. I didn't have Xbox Live then, but I loved the gameplay and the story, and you were always able to try different approaches in every situation -I remember I thought the plasma gun was useless, but it wasn't-, like switching weapons in some places or using a completely new set of weapons in every playthrough.
Games are so good and complex nowadays, that in some cases there are also a huge number of ways to make every playthrough different. Halo 2 was one of those games.
I also loved to download guides from the net and following them once I completed the game for the very first time. My favourite was this one for Legendary difficulty -by tomrace-, so well written:
http://www.gamefaqs.com/xbox/562116-halo-2/faqs/33420
I never do this anymore, but back then I enjoyed printing them or simply switching my computer on and read while playing. Those were the times.
I completed the whole game on Legendary, minus the Hangar part, which was literally impossible for me.
Concerning this generation, if I can recall correctly, I completed these games more than once; Gears of War, Oblivion, Call of Juarez -one of my favourite games this gen, more technically advanced than any other game Techland made after it-... I don't remember more now, it's late here and I should be sleeping already.
I am on my second playthrough in Halo Reach, and I would like to complete Far Cry 2 some day, because I love the tech behind the game. I never finished most games I have, so this makes up for every game I finished more than once.
Regarding Uncharted, I never played the series so I can't tell, but the game has some incentives like treasures and other stuff so it might be worth it finishing it a few times, especially if you enjoy the tech or Naughty Dog expertize.
p.s. the best ND game I ever played was that karts game on the PS1. I played it so many times with a friend in split screen...