Gears and Uncharted will still be enjoyed in the future as downloads because of nostalgia but the gameplay will be very dated. The cover system should be at least 10x better in 20 years, and will make gears and uncharted feel as clunky as movement in TR1 feels to TR anniversary. 

It all depends on what you grew up with, those are the games you'll want to replay in 20 years. I downloaded wolfenstein 3D and still enjoyed replaying it 20 years later with dual analog controls. The big change will be the multiplayer component. How will they feel in 20 years with a bunch of 30 to 40 year olds reminiscing.

In 20 years I will probably still be more inclined to play a remake of the space quest series or grim fandango then Heavy rain.

But really when thinking of a game that would it has to be a video game that is really good and a foundation for many games following it. Oh and it must of sold lots of and lots of titles.

Thats really hard, but only one game comes to my mind and that is Call of duty 4. It was a very good game, (even the cod haters like cod4, it sold lots of copies, and its been the foundation of majority of shooters following it when it comes to mutliplayer design and its not so good single player design.

Hmmm... difficult to say, but I think games that will still be played:

Portal/Portal2

Half-Life 2 + Episodes (probably because Ep 3 won't be out for ages )

Oblivion (I still periodically go back to Morrowind so Oblivion will likely be the same)

CoD4

Starcraft 2

and games that will be remembered for the right reasons (all of the above already count obviously):

Mass Effect series

Deus Ex: Human Revolution

Metal Gear Solid 4

Halo 3

Uncharted 2

The Witcher

Wii Sports

Mirrors Edge

This is pretty much asking "which are the best games today that rely on classic gameplay?"
Basically, games like SMB and Pokemon will still be playable in a quarter of a century because they're games that wouldn't be out of place in 2001 and will likely be as appealing as ever in 2021. So, regardless of whether or not they're perfect, you can't really improve upon them and they will therefore stay relevant.

Any fun, stylized game will be timeless. Ratchet and Clank, Sly Copper, any Mario game, Windwaker, etc.

For the relevant games... 20 years is perhaps a bit of a long time, but I only see Galaxy as a timeless classic. The game has tight enough controls that it will be enjoyable for a long long time and the game mechanism are unique enough that it will stay so for a long time too. I guess Portal could fit in here too as the game style is pretty timeless...
I can see a refreshed version of these in 10-15 years as making kids smile.

Games that made an inpact are a lot more numerous, but will definitely not be played by our kids: gears (gameplay), uncharted (redefined TR type games), Mass Effect (WRPG made popular (or is that Oblivion's claim)), CoD, Batman, SSFIV, Crisis....

Heck there are very few games that stand this test of time... Mario (2D), Sonic (2D), Metroid (2D), Zelda (2D), Tetris, Countrerstrike (simple gameplay and controls help) and that is much harder with 3D(polygonal) and the advances that are made due to system capacity both in graphics and the inherent physics of the game (HL2 was a physical evolution as well as a graphical one... Portal will reap the benefits of it, but HL2... only made an impact). Heck I can't find any other game that would be played if not because of the lag handheld have had to consoles (crono trigger would not be played and the DS remakes of DQ and FF are improved versions to make them accessible to non nostalgia prone gamers). There's no secret that my list is mainly 2D... graphics don't matter as much as gameplay in their age.

Bioshock,, Portal , LBP , HL2 ... I still think the gravity gun is one cool weapon , plus it put the spotlight on physics, I wonder still today how much of an impact the game had on Havok's success going forward, also it gave us a cool lady who was smart sexy without being a sexist stereotype strong but vulnerable .

A question, what games coming out do you think might make the grade ?

Well for Wii I think Zelda Skyword Sword and Metroid Prime 3

I think if Zelda's Skyword Sword is a good game and its motion control gameplay is innovative and used sensibly it will be remembered as another classic Zelda game that set standards for an action adventure that uses motion control.

I also think Metroid Prime 3 might be a classic because of its lock on control scheme. I can't see a dual controller stick controller without motion control or a keyboard mouse button control scheme replicating it as well and comfortably.

I'm not sure if Wii Sports will be a classic. It didn't impacted me as much as it did for the "casual" gamers and I can't see them playing it 20 years in the future similar to how I don't think people in their twenties or thirties think highly of Pong as they did when they first played it. Nor do I think they will feel the need to bust it out of their attic or basement to play it for fun but maybe for nostalgia yet even then I think they will do so as an afterthought. Wii Sports will be remembered as a significant game that help the Wii and motion control's success for at least the 7th generation, though.

It's quite funny how Pong and Wii Sports are so similar though.

Edit: Misinterpreted the thread's question.

 

I'm going with Mirrors Edge. Its basically in a genre all alone, i doubt it will be copied by others. Its graphics are simple yet look amazing. The few colours they used and simple design won't be overlooked in future gens as much as graphics heavy games like GT5 or Killzone.

The new Kirby that's coming out looks pretty kick ass imo.