NES: Ninja Gaiden (lots of fun times with this game but I still haven't beaten it and I lost the cart. I need to get another copy someday)
Well the prices only seem to be going up on the NG series games. They didn't really sell a crap ton of the second or third games so they are not only popular, but also scarce. Add in the fact that the people buying them now don't have much intention of keeping them a year or so and selling them again, and they are only going to go up higher in price the longer you wait...
For me this is a hard list to make. I think the only one that is easy to pick is N64.
N64: Goldeneye and Starfox64
SNES: FFIII (FFVI), runner-ups "Secret of Mana", "Chrono Trigger", FFII (FFIV), "Super Metroid", "Legend of Zelda: Link to the Past", "Street Fighter 2 Turbo", "Star Fox" all are very much in there
NES: "Contra", runner-ups "Legend of Zelda", "Mike Tyson's Punchout!", "Final Fantasy", "SMB:3", "Life Force"
And yes, I really mean "Mike Tyson's Punchout!" and not the later re-release "Punchout! with Mr. Dream". It just isn't the same game. There are a lot of hidden gems out there. I read that interview posted above and I definitely have to agree on most of that list, especially "Hover Force" on the Intellivision, although I will say probably my favorite Intellivision games are "Tron: Deadly Discs" and "Nightstalker".