When I was writing my epic thread on rpg.net about the 2nd edition Monstrous Manual (which you can download here), a recurrent topic was the idea of an "egg thief" game. There are so many monsters in that book for whose eggs the authors went into great depth about the number, prices and uses, that it seemed you could easily create an entire campaign in which the PCs were freelance or privateer monster egg collectors. All you would need is a big map containing lots of monster lairs and other locations of interest, places to make inquiries, and lists of potential buyers in far flung locations (the Sultan of Mandalaram, who collects hippogriff eggs; the Shogun of distant Yamato, who will pay 5,000 gp for a hook horror egg, etc.). And hey presto, you are up and running; there would obviously be more to it than just hunting eggs, but it's quite a powerful "high concept" for a campaign.
What the "egg thief" conceit basically is, is an excuse for the PCs to explore a sandbox beyond just "getting cash through adventure" - which is almost always reason enough, but a little bit thin. Egg thieving is a close cousin of "getting cash through adventure", of course (it ultimately amounts to the same thing in a more specialised way), but you can easily think of other purposes for messing around in a sandbox.
Because I am a lover of whisky, beer, rum, wine, and indeed anything else which has alcohol in it, and because I fancy myself to have something of an educated palate for the finer things in life (red wine goes with fish, right?) I have sometimes thought about something which I call The Oenophile Campaign,
What this involves is a map of an exotic fantasy world with all of the potential wine-producing (or whisky-producing, or rum-producing, or anything-else-producing) regions highlighted. The PCs are either themselves collectors, or agents working on the behalf of rich collectors, and their job is to sail the oceans, going from place to place in search of different drinks. Naturally, all these places are incredibly dangerous and full of weird and wonderful monsters and whatnot, and getting to the vineyards - guarded by ankhegs or blue dragons or on the back of a zaratan - is very difficult. But rather than being explicitly about killing things and taking their stuff, the aim is really about derring-do in the name of collection (while still implicitly being about killing things and taking their stuff, of course).
Such a campaign would probably be more like a game of Traveller than D&D in its spirit (pun intended). I'm picturing a huge archipelago of islands, a bit like in those Ursula Le Guin books, each with different varieties of wine or other specialist liquors (Creme de Urine des Ettercaps, anyone?), with the PCs sailing between them. A sort of D&D version of Hairy Bikers, I suppose.