My ongoing Tolkienian Science Fantasy project is all about creating an easy-to-understand "french vanilla" setting by replacing the common character and monster species of fantasy with some well-known examples from science fiction.
In personal communication, From the Sorcerer's Skull described the project this way: "I think this idea could broadly be placed in a category of setting creation: Make a D&D setting as derivative as possible, while employing as little as possible of the usual stuff D&D campaigns are derived from."
I think that sounds right. You get something different and distinct from a plain vanilla fantasy setting, but because all the pieces used to assemble this campaign are easily recognizable in their own right, the setting as a whole should remain easy to understand and remember.
Today's faction is the Lizard Kingdom, which occupies the Monster Island Archipelago, and the skeletal ruins of the once-great city, Necro-Tokyo.
The most numerous residents of the Monster Islands are the time-traveling Sleestaks from the original Land of the Lost tv show. The first Sleestaks to join the Lizard Kingdom were incredibly technologically advanced, although their numbers were few. But having found a haven for their species, and wishing to secure both their own past and future survival, these Sleestak scientists set about transporting other Sleestak communities from across space and time to coexist in the tropical region of the Archipelago.
Alas, the time travelers discovered that they represented the pinnacle of Sleestak science. Most of the other communities they found were stone-age tool users. The few remaining scientists are outnumbered by their machines, and vastly outnumbered by the temporally-displaced Sleestak migrants.
The technologically advanced Sleestaks might also be able to produce a class of infiltrators capable of disguising themselves as humans (or whatever other faction they're trying to subvert) based on the Visitors from the tv show V.
The mountain and desert regions of the Archipelago are patrolled by the Gorn, highly skilled and solitary hunters who gather to socialize only rarely. They're strong, intelligent, and cunning, with a keen understanding of stealth and ambush tactics. They have an ancestral hatred for humans and Apes, and owing to some famous historical encounter, prefer to arm themselves with bamboo-barreled rifles when fighting against primates.
If I wanted to add more variety to the Monster Islands' wilderness, I might add in some technologically advanced Dinosaucers, who are armed with high-tech laser pistols and bio-scanners and the like, and who can temporarily "dinvolve" into unthinking monstrous dinosaurs.
At the heart of the jungle, in the seat of the science Sleestaks' technological civilization is a compound that holds their greatest science leader, Kraid from the Super Metroid video game. Kraid sets the Sleestaks' agenda, directs their research, and reaps the rewards of their studies. Kraid is a genius and, thanks to some successful experiments, a giant. Kraid's political machinations and self-improvement programs are aimed at the eventual goal of seizing control of the whole of the Lizard Kingdom.
The revered, godlike ruler of the Monster Islands is, of course, Godzilla, from the original movie. Godzilla is the only living permanent resident of Necro-Tokyo. A city of ruined skyscrapers and abandoned pagodas, Godzilla patrols streets haunted by a thousand skeletons of the ages-gone human residents. The skeletons arise again each night to reenact a long-lost battle, led by the skull giant Gashadokuro. Each night, Godzilla wins again, and each day, he wanders amidst the bones.