Real world scientists have accidentally opened a tear in the fabric of reality, transporting their laboratory into the game world. Unable to repair and/or refuel their equipment in this (to their minds) primitive world they are now trapped.
The local band of 'nasties' (goblins / orcs / whatever) lives in relative peace with the local population.
Along come the PCs and go through their usual heroic monster bashing routine, wiping out the nasties and pinching all their stuff, then continue on their way.
Problem is, they don't kill ALL he nasties. The survivors want revenge and, after spending a few months recovering, start to take it in their own inimitable style (which is not unlike that of the PCs come to think of it).
Next time the PCs are in the area they find themselves VERY unpopular with the townsfolk.
A plague has hit the local area.
In humans it affects only the most vulnerable, the children and the very old, and even than it's little more than a summer cold. 24 hours of sniffles and then it's gone, barely noticeable really.
To sheep however it is fatal and the whole economy of the area is in serious trouble. If this keeps up the area could well be facing famine.
Somebody (enter the PCs) must find the rare herbs needed to make a cure.
Arkths or Ravagers: These are large landbound crablike creatures about the size of Grizzly Bears. They live partially in the astreal plane. Their food is magic. They can sense it at huge distances. Since spells and such are hard to eat (being in motion) and magical places are the equivalent of a sea of krill to them, they are looking for magic stashed in concrete places. Their primary food source is magic items, alchemical potions, and enchantments. They do a pretty good job of mangling/ eating the physical aspect of said items in the process of chowing down. These things will be the bane of dungeons everywhere, as they will slowly eat away much of the treasure (and the magical traps... so it can be advantagous to follow these things). Note: They will attack people with highly magical natures (i.e. high magic powers). They will probably kill the person in the process of sucking out the power.