Iji. It might not be the best thing in the cosmos, but it gets pretty darn close.
For various game maker programs, you can't go wrong with the Chzo Mythos series, assembled in the program Adventure Game Studios, or A Blurred Line, made in RPG Maker. Both demonstrate how you can make a mindblowingly awesome masterpiece on a limited platform if your writing and storytelling are in good enough form.
Edit: And of course there's Lugaru and it's upcoming sequel Overgrowth. Ninja rabbit fighting with intuitive context-sensitive input commands? Yes, please!
And Spelunky. Roguelike made into a platformer.
And Cave Story. Metroidvania platforming at it's best.
And yes, I have a folder full of these games. I'll add more in future posts if any particularly brilliant ones come to mind.
"What can change the nature of a man?"