If it had to be boiled down to one game and one game alone there is no doubt it would be Grand Theft Auto 3.
It has had a million variations on the core gameplay and is still being refined. It's truly the staple of the 128 bit era.
It's a type of Hybrid genre where they just constantly add more things for you to do and I see the formula sticking aroound and being succesful for a very long time.
I would have probably said the first Halo as it was one of my favorites (btw I hate Halo 2,3), but really when looked back on it wasn't revolutionary, merely done really well. Star Wars: Knights of the Old Republic also deserves mention I think, a very well done hybrid rpg.
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