Kirby’s Eternals posits that those classical pantheons were just misidentifications of a subspecies of humanity uplifted enigmatic aliens. In the fantasy context, maybe the aliens are some sort of elder gods (recall that Lovecraft’s Elder Gods felt unaccountably protective to the gods of the Dreamlands) and the Eternal stand-ins could be something like the Menzter’s Immortals. The other option would be to play up the science fantasy aspects for the full von Daniken. “A sufficiently advanced technology, etc., etc,”--maybe the world only appears to be a fantasy world and alien super-science is the order of the day?
Neil Gaiman’s Sandman strips down the pantheon idea with the Endless. Destiny, Death, Destruction, Despair, Desire, and Delirium are (as their names would imply) personifications of concepts. Marvel Comics has a similar (though less developed) class of beings like this: Eternity, Oblivion, Lord Chaos and Master Order, and again Death. The Endless fit into the mythologies of various cultures in various ways, but they don’t have mythology of their own really, just personal history. A group of beings like the Endless could be the sole deities of a world, just worshipped under different names by different cultures, or (like in Sandman) these sorts of personifications could be an order of cosmic beings separate and “above” the usual pantheons with whom PCs could interact.
“There came a time when the old gods died!” as Kirby told us in New Gods #1. As the title suggests, Kirby started in with the exploits of the New Gods--and Grant Morrison gave us even newer new gods in Final Crisis. A world could be post-god shift, adding some interesting background, or the setting could be in the midst of the “godless” period, post-Götterdämmerung but pre-reemergence of the new gods. Players might actually have a roll in finding/shaping the new gods that would appear.