Loosely adapted from a adventure seed in En Route (Atlas):
The PCs are among the third generation of their race- the gods recently demoted their last worshippers into animals and replaced them. The old races' ruins are still around and full of alien tools, materials, writing etc. The campaign is set around the idea of discovering what the old races were and what caused their downfall. Personally I would have humans/dwarves/elves as the old races and humanoid rats/racoons/pigs as the new. And only NPC classes.
Using some Mythos creatures from CoC in a very un-CoC campaign:
The Elder Things controlled South America when humans crossed the land bridge and encountered them moving south about 9000 years ago. They tried diplomacy, but the primitive humans were much too agressive for any meaningful relationship. So the ETs killed most of them off and genetically engineered the rest into a slave race (along with many of the animals the died off after the last Ice Age IRL). Fast forward to 1600. Europeans have discovered the new land and send ships to colonize it. The ETs observe this and are deciding what to do when a priest casts a spell. ETs fear magic- they have little defenses against it and send armies of slaves to crush the invaders both in the Americas and overseas.
The PCs are sucked through a mirror into a realm of shadow where the only people who exist are reflections of those in the "real world." The reflections only exist near mirrors and only when the real world person is near the linking mirror. Things of shadow also exist, but are fleeting and seem harmless.
An alliance of technology using gnomes and goblins have the rest of the races fleeing for their lives.
An invasion from space- using When the Sky Falls, meteors fall and destroy most of the surface cities. Ethergaunts with illithid slaves march out of the meteors to conquer. Or will'o'wisps inspect the whole planet. Or plague survivors seeking help and in their insanity, spread the disease.
A desert campaign where gnomes rule. They have capped wells, springs and oasi (sp?) and distribute water as they please. They are very serious about keeping their monopoly on technology.
For Alternity, but still useful here:
http://alternity.net/onlineforums/index.php?act=ST&f=26&t=302&
) in an effort to find out the cause of the problem. Along the way, they meet other travelers either seeking the same thing or looking for a way home, agents of some 'otherworldly' demonic force, and the inhabitants of the other realities (mutant Soviets, Nazis, despondent survivors of a nuclear holocaust, etc.).
