Deus Ex - Greatest all round game ever developed. Technically, gameplay, story, sound...you name it, this has it.
Super Mario 3 - This was the turning point for platformers of the time and what they are now.
Half Life - Introduced epic shoot-out moments to fps games, one of the biggest advancements either.
System shock 2 - Should be further up, as a fps/rpg hybrid second only to DX.
Morrowind - A masterpiece of old school rpg and in-depth world lore.
Mario 64 - Original and still the greatest 3D platformer ever made. Will never be topped.
Zelda: A link to the past - Utter beauty.
Elite - Another original and still the best moments. Even from the 80's.
Paper Mario 64 - Amazing game. Super Mario RPG introduced Nintendo to square, this though was the pinnacle of that series to date. Play it.
Zelda: Ocarina of time - Say no more.
KOTOR: Best star wars game that isn't academy.
FF 6: Absolute masterpiece. 7 appealed to the masses, and the later ones did good things to the magic system, but this was the finest hour.
Thief 1: Still one of the best sneaking games to date.
Goldeneye: Obvious.
Halo 1: Moved the genre forward much like HL1 did. The last big A.I leap too.
Turrican 2: In this age of graphics over everything, Turrican reminds us that you can be technically superior to everything else in all ways, and still create genre defining moments that last.
Super Metroid: One of the 16-bit era's finest moments.
Streetfighter 2: Talk about basically starting an entire genre. Yeah there were previous fighters, but this just moved everything forward in leaps and bounds.
Eternal Darkness: Still one of THE most underrated games of it's time.
Psycho Fox: Yeah Mario 3 and Yoshi's island and the likes took platform gaming to a whole new level each time, but this game still stands shoulder to shoulder. It's 'sequels' are worth a shout too.
And a shout out to Alan Wake which I just noticed made it 21 sadly
One for this generation and criminally overlooked.