1) Riftwar scenario - a powerful force beyond all comprehension or hope of defeating has invaded your world and is consuming it utterly (Tharizdun, Galactus, Cthulhu, whatever), while your greatest gods fight a holding action, your epic party must seize as much of society as possible and move them to a safe place, elsewhere in the planes. The inhabitants of those planes won't likely be too happy at the sudden arrival of the surviving refugees from your lost world, and they must be dealt with somehow as well, to prevent the extinction of everyone from your world.
2) A growing Darkness - the plane of Shadow has long been seen as a dark and twisted reflection of the material world. It has grown more dark and dangerous, and spells to travel there are no longer safe to use. Undead shadows grow prolific, and attempts to eradicate them seem doomed to failure, as there are always some that dive into the ground and get away from attempts to destroy them. Society itself seems to be breaking down, and scrying has discovered a horrible thing. Fiends now walk openly in the plane of Shadows, and they are somehow infecting the shadowy duplicates of material people with some fiendish taint that carries over and taints the material-plane dopplegangers! As people's 'shadow-selves' become warped and twisted, they too begin to turn towards evil, and child-bearing women whose shadow-selves have been demon-touched give birth to Tiefling babies! The party must travel into the Shadow plane to try and stop this fiendish plot, but discover that it's to late. Purging the fiendish taint from the shadow-self causes it to die, and, in the mortal world, the corresponding person loses the will to live and dies shortly thereafter! Portents of doom begin to appear, and the epic party learns that some of the gods themselves are hastening the end of days, because they believe that the only hope now is end this universe and start over!
Does the epic party help the gods to destroy the universe, while the fiends of the pit attempt to stop the apocalypse (We were winning! You saw! We were winning...)? Do they side with the fiends and attempt to stop the impending end of days, believing that they've found another way to stop this merger between the fiend-tainted Shadow plane and the Material plane?
If there is a third option, will it involve the god of the sun giving his life, explaining his decision to end the world and start over, rather than commit suicide?
3) And he wept, for there were no more lands to conquer - 30th level and nothing to do. Bored. Epically so, even. And then the new universe is found during some Epic research, a world much like the Material plane, but inhabited by *things* too horrible to contemplate. They came from the stars and conquered this world aeons ago, and whatever man-like races once thrived in those cyclopean ruins are now gibbering mad things that howl and caper before their writhing oblivious alien masters. The Things have made some incursions into the Material plane, but never seriously, and the world certainly is in no danger, at least, not yet, but the rulers have come to the notion that perhaps this world can be taken *back* from them, and the monsters not just reacted against when they invade, but bearded in their own den... The Epic party is asked to invade this world, with their armies of followers and troops provided by a coalition of allied rulers, to secure first a beach-head, and then finally, to reclaim this lost world entirely for the races of man, driving the tentacled monstrosities back into the cold depths of space!