Another registered user created out of the primordial ooze that is the Horde. Glad you joined!
I am sarcastic to my first answers went the wrong direction:
Defeat him with unconditional love. Accept him for what it is and make him cry and go away in confusion.
Have your characters combine to create a super-being ala Voltron that has enough power to beat it back enough to allow the world safety for a few centuries.
Then I thought, if the players have a bloodline of power, perhaps that power comes, in part, from the previous pantheons. In that case, maybe the remnants of the destroyed gods still lurk (can a god truly be destroyed) and they have been pooling their power. In a climatic battle the players end up being destroyed, but at that moment the old gods each choose one as their champion and send their last bits of power to them as they are engulfed in the void. From the inside they get this power and are able to do something huge and heroic that severely weakens this evil.
Or start making their powers increase and new ones evolve at critical points in challenges that give them the power/knowledge to halt certain aspects of the creeping doom. Evil will at some point notice and taking an even more active role in trying to defeat them which grants them even bigger powers. If it is the end of the world then it might be fun to let them be uber powerful to give them a perceived chance at defeating the evil. Then let them sacrifice themselves and their power to save the world.
Then again, evil can win, the earth is engulfed, game over for humanity. Not all stories end happily.
I have never played a game that high powered, but if I did, I think I would cream myself if I got godlike powers and was able to use them, if even for a short time. All that power, the things I could do. Move the planet to a place that would force the evil to move on (who knows those books

), create a weapon from something in space that the creature seems to have always avoided. A dark comet or something holds its kryptonite and once they have appropriate powers they can notice this and harness it. Protecting humanity in a bubble of force as mentioned, they would have to stay there but they would be safe at least...for now. Perhaps it is limited to the outside of the planet, so they hollow it out and the survivors would have to become underground dwellers till the evil moved on.
I think you have the opportunity to go to crazy town and you should take advantage of it.
Sounds AWESOME!!