Ever since I picked up MMV, I have wanted to run an Eberron game but that draws heavily upon sci-fi / horror and urban fantasy movies that have modern settings.
Essentially, the PCs would be part of a government-funded secret organization dedicated to the policing and hunting down of Aberrations, Outsiders, and other nasties in the city of Sharn (essentially, the Men in Black meets Hellboy and the B.R.P.D.)
In one of their early adventures, they would be called in to investigate a string of murders where the victims' body parts have been systematically harvested, never the same part twice. This would put them on the trail of a Vivisector living in Sharn, and would draw heavily upon the movie Jeepers Creepers (which I think probably inspired the creature).
The campaign would eventually ramp up to a lengthy battle against the Mind-Flayers of Thoon, who have been sending their construct Soldiers and Scythers to attack a teenage heir of House Cannith, who unbeknownst to him, possesses an heirloom which contains within it, "Quintessence", which the Thoon seek. In fact, the object he has contains within it the trapped soul of a giant from Xen'drik, the original creator of the Creation Forges, and the "father" of the original Warforged. The boy is likewise being stalked by a group of well-meaning Warforged who believe that he holds the key to their origins and the potential for the future of their race in his hands. (Plot stolen wholesale from Michael Bay's Transformers).
Somewhere in there I would also like to use:
Mockery Bugs and their Ankheg progenitors in a combination of Invasion of the Bodysnatchers and Tremors.
A Nimblewright working for the Emerald Claw, much like the "clockwork nazi" from Hellboy.
Relatively peaceful encounters with Elans, Thri-Kreen and other odd-ball races living and working in Sharn.
A creature that emerges from an artifact brought back from Xen'drik that stalks a museum at night (The Relic)
The female of an aberrant race that requires humanoids to reproduce (Species).
A Government conspiracy involving the colonization of Khorvaire by the Quori (The X-files)
There are probably other ideas I could spin out, but that is all that comes to mind at the moment.
Robert "We're the Ones Who Bump Back" Ranting