1. In the year 2083 a limited form of time travel was discovered. While you could use it to travel back and forth with relative ease, it always sends you a certain number of years back, namely 162.7 million. Several competing supercorporations send small armies of personnel in to harvest resources and eliminate the competition in more direct ways. However, two years later all the portals back home suddenly stop working, and suddenly over a thousand high-tech scientists, engineers and military personnel are stuck in the jurassic era with an environment that has been warped by their hazardous experimental resource-collection methods.
2. The players are a group of children (10-14 years old) in a rural mountain community. They are forced to flee when raiders attack and raze their mountain community, then after a period of running and hiding encounter a group of ancient beings who had sworn to protect their community in ages past. It's been a century since they were last needed, and these beings (1 for each player) arrived too late to save the community. As such, they have tracked down all there is left to protect- the children. Players each control 1 child and 1 guardian; 1st order of business is probably to attack the raiders, but where do they go from there?
3. Players must escort a large, strange animal vast distance, say across a continent; the fantastic creature has great religious, cultural and/or practical value, so hazards include plots to steal or harm it in addition to the normal dangers of the areas they're traveling through. The creature is semisentient, and caring for it/staying on its good side are important aspects of the campaign.
4. The players are all basically heads of Vecna- High-level characters whose preserved, severed heads can be attached to freshly decapitated bodies. The bodies, however, only last a day per character level before turning to dust, returning PCs to their default state as unconscious minor artifacts. What do the players do? They could actively seek to remain “alive”, acquiring new medium-size humanoid bodies through any means necessary. . .or they could spread word of their nature and live through the ages as artifacts. A valiant soul might give their life to that a PC might use their body to fight some great evil- or a less scrupulous individual might use the body of another and attempt to bribe or manipulate the PCs. Either way, at some point a PC should definitely find himself attached to the body of some moronic adventurer whose compatriots are watching expectantly, thinking that they're Vecna.
5. The players are ghosts in the modern day, based in a classic haunted house in a rural neighborhood. They gain xp from scaring the crap out of people, and leveling up lets them influence the material world more and more directly as well as journey further away from the house (at level 1 they can't even go outside unless they've taken a feat or talent or something).
6. The characters are trapped in a large, abandoned castle by a dragon that's way too powerful for them to consider attacking. The dragon does not vocally communicate and is clearly intelligent, but will not damage the castle and attempts to eat them whenever they emerge. Players must attempt to figure out the mystery of what's going on while dealing with more immediate concerns like finding food and determining who or what is keeping the place so ship-shape. The castle is full of well-concealed secret passages, including some which lead to underground complexes, both natural and man-made...
7. Players are a traveling D&D band that has adventures as they tour the world playing for their fans- everyone's a gestalt Bard/whatever. A healthy dose of cheese is intended here. It doesn't have to be a rock band, if you really don't want to. . .
8. The players are incredible warriors hailing from ancient times. They live today due to the dying curse of a god-king whose defeat they caused; eternal life combined with the compulsion to eternally wage war. They're extremely high-level but not superhuman except for how their bodies always knit themselves back together afterwards (regeneration 1, no bypass). They've been fighting aimlessly for years, but now they've come across some hint of how to break free of the curse's control- and when beings such as these have a cause, woe to any that would stand in their way.
9. The military is losing the (realistic/mundane) war. But they've discovered dragons in subterranean caverns and have been breeding them. The PCs were hotshot soldiers with histories of discipline problems. Now they're guinea pigs who get to try flying these things into combat. Oh, and the dragons are quite intelligent- you wouldn't notice it much since they've been raised like animals since hatching, but wait till they start learning how to speak by listening to the PCs and mimicking them.
10. The players are dragons who have slept for 500 years and now awoken to find a modern-day city built over their lairs. They can all shapeshift and take on human form, though fitting might be just a little difficult.