Maybe it's a controversial choice, but I'd like to nominate the epic No More Heroes. Regardless of the humor and sarcasm, the storyline was actually brilliant, because it was a fantastic mockery-cum-tribute of various modern cultural phenomena: games, porn, anime, movies, wrestling, superheroes, Star Wars, action movies, fake French accents, lightsabers, cliché storytelling, GTA, racial prejudice, motorcycles, technical superiority - it's as if the game tells a lot more than just what is said and done in it.
Feel free to disagree, but I hope you can follow my reasoning.

Another one on which opinions seem to disagree: Tales of Symphonia. To me, it was just epic, handling issues like the role of religion in society, religious suppression, life and death, genocide, racism - it even had some (unintended?) parallells with the more human side of World War II.

And last but not least, the entire Umbrella story summarized in Resident Evil: The Umbrella Chronicles is nothing special when you just look at the main events. However, it is the eye for detail that makes this series stand out from its peers, with as a pinnacle the genius personality of Albert Wesker. Every event has been worked out from every possible angle to make it all fit: they never needed to, but it does make the series special.

 I would also gie a point to Team Ico's games.

Fabulous 

Yeah, I think what set FFVI apart for me was that they threw so many characters at you, but yet developed pretty much all of them to the point you cared. From the feral child Gau, who would be a throwaway character in most RPG's, to the train ride with Cyan's dead wife and child, (it may have gotten a little dusty in my living room when the train pulled away with one last sad pull of the whistle) you really got attached to just about everyone in the game.

Others I'd second would definitely be Psychonauts and Portal.

I'd also throw Dark Cloud 2 into the mix. Pretty much every aspect of that game was perfectly implemented, from the georamas to the combat, weapon evolution to photographs/inventions, there was a lot to wrap your mind around if you wanted to put the effort in. The story wasn't anything too terrific, but the gameplay from top to bottom is almost unrivaled. (It's also one of my favorite games of all time, and a third installment would sell me a PS3 almost immediately if it were announced.)

Other than some that've already been mentioned, I liked Darwinia's story.

Heh everyone's wrong the smartest game ever was Earthbound, so many hidden little things in the text it's funny for everyone (ok ok yes I'm being a Earthbound fanboy =( sorry) The design for Chrono Trigger is obviously smart and a great branching story to go along with it. I'm currently downloading Portal but so far it looks very smart. A lot of the PC games are smart, either in gameplay (starcraft), or story (half-life), or just awesome (many point and click adventure games on PC).

One last one that hasn't been mentioned ZACK AND WIKI (BUY IT!) The puzzles are very smart at times.

Super Metroid

Interesting choice. I can't really say I disagree.

 I'd agree if for no other reason than the boss fight where you can fry the big underwater dragon thing in like 5 seconds by hooking your grappling beam onto one of the exposed electric things while it holds you. I remember randomly discovering that playing with my brother and we both about shit ourselves it was so awesome.

If Super Metroid gets the nod than I'd suggest Prime should as well. The atmosphere, graphics and world design perfectly portray the sense of isolation and aloneness, while the scanning allows for a deep story if your so inclined. It's just a very smartly developed and put together game.


but I'm still trying to think of a truly "Smart" game that isn't a puzzle game, or at least very puzzle like.

Argh, I kinda have to agree with you on Prime.

I still hate the game, though.