I've had this idea I am going to run soon, but maybe one of you wants to give it a go as well.
Short version: why not every time?
Long version:
Somewhere 15000 years ago, humanity is starting to really get off the ground. But there is this danger everywhere, a creature unlike any living thing, vicious and dangerous and deadly. The shamans call it "the hunger", because it consumes everything that gets in its way. And, well, they had very limited vocabulary. One day, 13 tribes come together, their shamans preparing for one big ritual that will seal the hunger away forever and allow humanity to prosper. The ritual is long and cruel and bloody. Several children are sacrificed to lure the hunger into the ritual circle and the shamans all spilled their own blood to finish it. They knew they could never kill it, so they didn't try. They sealed it away into an artifact, where it would never be able to do any harm again. Or so they thought.
Through the ages, the artifact is popping up over and over again, turning kind people into madmen, love into hate, kings into tyrants. Always drawing in luckless adventures to turn fate for the better. Until you get to the final conflict, the time when the hunger will be challenged and destroyed forever, right here in our days. Or maybe even (pause for dramatic effect) in the future?
Start out with early humans in their tribe, 3 refresh, 10 skill points (just a suggestion, of course). Once the ritual is completed in the first episode, jump ahead a few thousand years, to whichever time you like and have the artifact pop up there, with new characters to battle it. Only each time you jump means a major milestone, so the players can build increasingly powerful characters. Sometimes a character will be the descendant of one you played earlier. Sometimes you may play the same wizard with 200 years difference and a few characters inbetween. The possibilities are endless.