I've been watching a lot of Red Dwarf recently. That combined with Barking Alien's link to some of his weird campaigns, inspired [Note: Use "Unspired"] me to come up with this:
In the distant past, an alien ship crashed on Earth. Their "engines" were destroyed, but other systems remained intact. Luckily for them, they got here just as the first ape-like beings were appearing. They were able to genetically engineer us so that we would be adaptable and intelligent. Combined with natural selection, and the culling of non-useful strains after a certain point, (monkeys, lemurs, and the great apes were left around so that they would have a "clean slate", so to speak, if they had to get rid of all of the current lines). They needed us to be able to manufacture the parts, as the damage couldn't be fixed at the time. Fast forward to the world of Shadowrun. 80-90% of these aliens have become unintelligent (compared to before that is...). The remaining 10-20% have been taught how to blend in, and have been taught from an early age that fixing the ship is the most important thing. They've also kept good records - they don't worship their craft, or something like that, and everyone has a good working knowledge of how it works, sort of like the standard knowledge that most humans have of an airplane today. We're just about able to manufacture the bits they need. The problem is, they need some sort of food source, and they eat mental and emotional energy. They survived off of a small group of hosts until they'd altered the humans enough to be able to feed on them. Now, some of you may be saying: "So? Do I really use all of it? Why is it such a big deal?". Because it causes depression and schizophrenia. Here's the thing: They're cats. Not all cats of course - that 80-90% that mutated no longer feed on people, but the rest do. Haven't you ever wondered why the "Crazy old lady with her dozen cats" is a stereotype? It's because rather than the cats being a symptom, as was assumed, they're the cause. You are a group of 'runners who have done a few missions for various Mr/Mrs. Johnson's, and you've been approached by a mysterious orginazation who needs your help in dealing with it. Not great for dumping into something else, but it sounds like an interesting short campaign.