Premise: The Conspiracy is after the Heroes.
It's a common plot for RPGs. It works for D&D or Trinity; Deleria or DC Heroes; Vampire or Cyberpunk; Puppetland or Sorcerer. It's also a very common plot in movies and theater - taking various forms from The Bourne Identity to Who Framed Roger Rabbit.
What is the most interesting thing that can happen? The most interesting chapter of the story? How does it begin? How does it end?
This post is really just a group brainstorming post, so we can benefit from each other's creativity. Maybe we'll all be able to inject something fresh into each other's game.