I'll resurrect this from the dead to post my thoughts on the rarest games, since trends seem to have fluctuated over the years:
Top tier:
Sonic the Hedgehog (US UPC)
James "Buster" Douglas Knockout Boxing
2nd tier:
Strider (US UPC)
Super Monaco GP
Dick Tracy
3rd tier:
Aerial Assault
Joe Montana Football
R.C. Grand Prix
4th tier:
Golden Axe Warrior (US UPC)
Spider-man (US UPC)
Power Strike
Moonwalker
Ghouls'n Ghosts
5th tier:
Alex Kidd in Shinobi World
Slap Shot
Castle of Illusion
I've still yet to see a US Strider on eBay (message me if you have one!), and I've been looking straight for six months. Same goes with Sonic (although with those prices, I'm not sure I want to). Castle of Illusion's rarity, I feel, is quite overrated by the DP guides - I've seen a fair number of copies online and in B&M stores.
It's funny how the market has changed - someone saying they got $50 for a Super Monaco GP in 2004, while the mint one I sold on eBay a couple months ago barely pushed $10.
Of course, ranking the re-releases on that list is opening up a whole new can of worms. Still, some modern discussion on this would be nice!