I'm riffing on the Dimension X campaign in D20 Future, mixed liberally with ideas yoinked from Dr. Who and the comic book Planetary. Except for the addition of the Madness Meters from Unknown Armies, I'm using the rules as written.
PCs are operatives of the Hoffmann Institute (faction from D20 Menace Manual--"for the benefit of mankind" vs. Fortean weirdness sums it up). First episode, dispatched to New Mexico to investigate strange em-band pulse emanating from the desert near Roswell.
Deserted base, airstrip, broken windows, tumbleweeds. Underground bunker with a massive secured chamber, but inside...as the ceiling lights boom into life row by row...only a single slim glass-enclosed ATM booth with tinted windows in the center of the empty hangar. Meanwhile, up above, an Apache blackhawk settles upon the broken tarmac and special-ops pour out.
PCs look in the booth, finding it much larger inside than out--that's their TARDIS, with nary a Gallifreyan in sight (I'm considering the only denizen of the machine as a talking German shepherd--the Learned German Dog). In the ensuing firefight with special-ops (sent by whom, I wonder...?), the TARDIS activates and with a high-pitched hum rotates itself out of this dimension and time coordinate.
From then on, all time periods, dimensions, worlds, fictional worlds, game settings, cities, oases, and what-have-yous are fair game. I don't think getting home will be a problem (no Sliders- or Quantum-Leap-dilemma here), but the PCs will slowly discover evidence that theirs is not the only TARDIS. A mysterious group known as the Four is attempting to manipulate events trans-dimensionally with the goal of affecting the Apocalypse/Rebirth scheduled to take place in December of 2012. The PCs will have to stop them.
Of course, it won't help that the PCs have tried to stop the Four already. They lost. They were implanted with memory blocks. They were told that if they came back, the game would stop being interesting...and start being annoying. They were told that they would suffer and die if the memory blocks failed.
If only they'd remembered that detail.