I guess I'm one of the oldskool PC-crowd here, so for that reason I'm going to say UFO:Enemy Unknown. Well, that reason and of course it was a fantastic game, it had pretty much everything you could hope for:
-destructible environments in tactical combat that is so challenging and rich in variety that I have yet to see any game beat it
-strategic management of your military bases while trying to balance the budget and choose which countries to please the most
-alien tech to research
-many different aliens to fight against
-as mentioned, mind controlling aliens *shudder*
-and lots of more, go get it and play it through. If you can, it's no walk in the park.
Now, if it weren't for UFO, I'd say Star Control 2, but my mission now is to get UFO as high up on the list as possible :)
