I have two Genesis carts in my collection which I have heard are pretty hard to find.
Joshua: The Battle Of Jericho (yes, it's by Wisdom Tree, the same people that bought you Bible Adventures on the NES) is believed to be one of the rarest Genesis carts. I found one at Gamestop for 63 cents (it was marked at 89 cents before the 30% off clearance).
Rolo To The Rescue isn't as rare as Joshua but pretty hard to find. I got mine for 99 cents at Gamecrazy. I heard it was a decent platformer. I haven't gotten a chance to play it since my Genesis isn't hooked up at the moment.
Another rare game, which I don't have (and have never found in the wild) for that matter), is Action 52. But the only reason you'd want to play it is to see for yourself how one company could not only make one, but 52 games that blew. "Quality over quantity" comes to mind. :lol:
I don't think any of these have much demand, but if you find them, especially for as cheap as I did on Joshua and Rolo, it's not too bad.