MARIO PAINT! If there is one game that begs for a Wii sequel this is it.
A quick search of Wikipedia reveals that it did in fact receive sequels, but I contend that they don't count because they were (A) Japan only and (B) on the N64DD. I mean, come on, to be any more obscure it would have to be an unreleased Virtual Boy game.
It has all sorts of creative possibilities and minigames, and the use of the SNES mouse is a lot like the pointer. It was a Wii game 15 years before the Wii!
P.S. There's a guy on YouTube by the name of TomBobBlender. He redoes video game music on this video game, it's awesome. I especially recommend "Mega Man 2: Dr. Wily's Stage 1 Theme" and "Final Fantasy Four Battle Theme". http://www.youtube.com/profile?user=TomBobBlender
[edit: And can anyone who's played the fly-swatting game honestly tell me it wasn't the best thing ever?]
[edit2: Robo's theme, from Chrono Trigger, as done on Mario Paint. Made completely out of win. http://www.youtube.com/watch?v=SPnwmAdr8hE&mode=related&search= ]