My vote goes to UFO: Enemy Unknown, Pirates! and Elite.

Oh nope, changed my mind. This:
https://www.youtube.com/watch?v=h6DtVHqyYts

oh and NSFW language

Star Control II

My personal favorite is The Pandora Directive.

Go ( baduk / weiqi)

Blade Runner as I, uhm, might've mentioned a couple of times before. I'm a bit like a broken record in this regard :P

most memorable part for me : Stepping out on the balcony of your apartment and hearing this : Blade Runner blues
gives me the chills just thinking about it.

W-what sequel? Did they ever announce anything? Also, that game wrapped up so neatly; it's hard to imagine what they would even do for a sequel.

Kirby's Adventure!

"Smashing Pumpkins Into Small Piles of Putrid Debris" a.k.a. "SPISPOPD" wins hands down for me. :)

Indiana Jones and the Fate of Atlantis

I'mma let you finish, but Gothic 2 is one of the best video games of all time.

There are a bunch of games that I absolutely love, such as Morrowind, Silent Hill 2, Baldur's Gate 1/2, Arcanum, Planescape: Torment, Vampire: The Masquerade - Bloodlines, Fallout 1/2, the "Souls" games, Raven Shield, Homeworld, Freespace, and Thief 1/2.

But when it has to come down to one, it's always going to be Deus Ex.

Monkey Island 2 and Eye of the Beholder 1.
I do a playthrough of these two almost every year.

Half-life 2
I'm not the greatest expert in games (I've never played Plainscape, Mario 3, Deus Ex or Ocarina of Time) But in my short gaming carrier I can't think of a single game that was so perfectly put together. It's shines quality and care like a Michelangelo painting or a Beethoven symphony.
Gaming has the advantage of making things happen to you. And while Half life 2 offers you no RPG-style choices the whole thing is designed within a inch of it's life to being your story. It's beautiful.
Bioshock Infinite makes second place for me.

I assume you mean video game? I would have to go with the original Civilization or Colonization.

If you mean any game, based more on the ridiculously good times I had playing it with friends and hated enemies more so than the game being great, I would go with Axis and Allies.