When one thinks of Dungeons & Dragons, one of the primary concepts that comes to mind is that of slaying monsters and taking their treasure. The entire experience/level progression system has traditionally been based on this idea (though later editions of the game have expanded to include more non-violent means of progression, which I appreciate). One of the things that breaks up the monotony of this concept is the wide variety of monsters that one's character may face.
So why not base an entire campaign around this idea? You know it's going to happen anyway, so why not acknowledge it from the beginning?
The concept of the Monster Hunters campaign is simple: the PCs are a band of monster hunters. See? Simple. Now, while the idea of traveling around being more or less philanthropic, aiding villages with their monster problems, is certainly a worthwhile concept for a campaign, I'm thinking of something a little more focused.
I have a number of supplements and magazine articles - many of which date back to first edition Advanced Dungeons & Dragons - that examine D&D's concept of material components. Material components (known in some games as reagents) are physical items that are necessary for the casting of a spell, and often are consumed by magic in the casting. Many of these components are rather exotic - the eyelash of a cyclops, the blood of a wyvern, that sort of thing. So wizards - especially high-level ones, with all of their powerful spells - have a fairly constant need for the acquisition of these items. But frankly, when you become such a high-level wizard that you're in need of such items, you've got far more important things to do than grub around for components. World-saving things, plane-hopping things. That's where the PCs come in.
The PCs work for a powerful wizard or alchemist. In Middle Earth, this might be someone like Radagast or Saruman; in the Forgotten Realms, it could be Elminster or Blackstaff. Their job is simple: the wizard tells them that he needs an item. He may or may not provide the PCs with information about where they can find it, descriptions of the beast or item in question, etc., depending upon the tastes of the DM and the needs of the adventure. The PCs may just be simple muscle, but frankly, I'd find it more interesting if part of the reason they were hired over garden-variety mercenaries was because of their supposed expertise in the area of monster lore.
Part of the adventures would likely involve doing research. This could mean anything from journeying to a large metropolis to find a scholar who catalogues beasts, to venturing into the trackless wastelands to find a hermit-sage who knows more of these creatures than anyone alive (or may be the only one who knows anything certain about them). It may mean going to settlements where the beast in question was spotted and asking around for witnesses to its appearance and behavior, or just plain trying to find the elusive creature and observing for themselves.
What gives this campaign variety, of course, is the monsters themselves. It might be helpful to bear in mind a model something like "Buffy the Vampire Slayer", which operated mostly on a "Monster of the Week" structure for its episodes. Of course, in that case the monsters were the ones who came to town, whereas I'm imagining something where the PCs range out from a central location (the wizard's tower) to various locales in the countryside. In any case, the wide variety of exotic beasts in the many Monster Manuals and their ilk should provide ample fodder for adventures. The DM chooses a monster to focus on for this adventure, taking into account what makes it unique. Then the DM figures out what it is that the wizard needs from this particular monster. Sometimes it's going to be something really esoteric (such as the creature's dreams, or its laughter, or something), but most of the time it'll probably be a bit of its anatomy. Then it's up to the PCs to learn as much as they can about the monster - through research, interviews with witnesses, and/or trial and error - and slay it. Or capture it. Or do whatever is necessary to get that bit from the monster and survive the encounter.
Now, while it stands to reason that the PCs are working for a powerful wizard and thus they can rely upon his powers to save their bacon if things get too bad - after all, they're working in his interest - I wouldn't use this safety net. As I said before, this wizard has big, important things to do that take up his attentions. To him, the PCs are NPC Hirelings, not allies. If they get slain, that sucks for Elminster only because it means he has to take the time out of his busy day of drinking with Mordenkainen and seducing goddesses to ask Lhaeo to hire more monster hunters. Don't expect him to show up at the funeral, is what I'm saying. The PCs are largely on their own. Yet, for those DMs who worry about such things, it's at least conceivable that the wizard can pop in to save them if a deus ex machina is all that stands between the continuation of this campaign and a Total Party Kill.
To keep this campaign from getting stale, the DM can introduce subplots into the adventures. Perhaps a local villager feels protective of the monster. Maybe the monster is a shapeshifter and has replaced someone influential in the region. What if the monster has the ability to possess people, or to make them do its bidding? Perhaps a cult has arisen around the monster, providing it with tribute and sacrifices, informing it of local activities, making offerings in exchange for its protection? Maybe there's a local feud between families that makes any business in the village near the monster's lair difficult? You can have subplots that are completely unconnected to the monster hunt, but which nonetheless might draw the PCs into them...
Given how many monster compendiums are floating around out there, this seems like a campaign that you could run for years and years.