Hmmm... hard decision because I'm kind of a connoisseur in case of original and unique games.
My personal favorite would have to be X3 which while not being the only "space sandbox" game (there is freelancer and... and something else I'm sure) it's the only so VAST and perfectly designed, You can do whatever you like build your stations trade for the entire game end never even ONCE shoot a blaster, or you can totally ignore trading aspect and just become a merciless pirate. You can do whatever you like and that's why I love this game.
other game of the "unique" type would have to be Daggerfall. Yes I know that it's in fact "Buggerfall" because of the amount of glitches and bugs this game has but it is so fun! When you realize that the game world is HUGE and you can do anything you want it gets even better. While in the TES series I personally like Morrowind the most (oblivion is just... empty) Dagerfall has a special warm spot in my heart for being foolishly brave and exponentially fun.
Third game I will mention is Mount & Blade for its pure fun factor. And as far as I know it's the only real "knife simulator".
Last (but not least) of the games I will mention (since there are soo many more) is Hearts of Iron...
Yeah I know that's unexpected but there is something enduring in just building your country for world domination in a way that is not friggin easy

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As said these are not the only unique games in the world, hell there are many more like Psi-ops, Scrapland, Startopia, Sniper Elite, Thief and Dungeon Siege.
But those mentioned are closest and dearest to my soft gamer heart

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