Just had a thought inspired by Dean. In a FLAILSNAILS game he was part of a party that defeated a crystal dragon and earned "billions" of gold (Dean's words, no idea what the actual tally was). Anyway, this thought popped into my head.
A sandbox campaign where there were only dragon lairs as adventure locations. Of course, there would be other guardian beasts, symbiotic creatures, or worshiping cultists/humanoids in some of the lairs. But each and every place where you could earn XP through slaying creatures and taking their stuff would be a dragon's lair of one sort or another.
Low level PCs would strive to just get in and make off with a bit of loot and their skins. Mid-level PCs would then try to take out some of the younger/weaker dragons. High level PCs would - well, whatever they want, pretty much.
It would likely be a harsh campaign, as the risks would be very high, but the rewards commensurate. Could be fun.