I've run one-shots based on the idea that the players have recently purchased a "Monster Hunting" guild frachise and have set up their business in a city. Every episode centers around a different monster.
The only time I've run this I had someone hire the players to hunt down a vampire near the docks. I used a Chelicera, which is a blood-sucking spider that has mimicry abilities as the supposed vampire, and the players spent most of the adventure trying to sort this all out.
Other monster hunters ideas I've had:
* A noble purchases a hippogriffin with the idea of taming and riding it. Unfortunately the beast has proven too much for him and he now seeks to get rid of it
* A mysterious merchant is selling miniature versions of monsters to children with wacky results
* Black dragon hunt in a swamp
Besides the monster hunt aspect, you can always throw in local politics, rival adventure bands, and the like. ENWorld Publishing has a book on this in their shop.