Just thought I would free form some ideas and concepts since the weather is going to be bad all weekend... Probably won't go to the first day of Ren Fair if they don't cancel it anyway.
* first thought I start with the midwestern expansion of the rails as a base. I'd like it to be set in space though so we get the equivalent of a railway which would be beacon pontoons set up to keep warp engines on course through space with the ship moving between pontoons at 10 times the speed of light. With a warp equipped ship the actual vessel can look like anything as long as it fits within the warp bubble. So we can create space trains with really elaborate hulls. The tracks need to be set up though which requires crews risking getting lost in space to lay down the beacons or follow tracks set up by an automatic system into unknown territory. It could take hundreds of years to travel between Earth and the edge of the frontier.
* Cyborg elves in a nuclear apocalyptic wasteland. Why yes I've been reading Shadowrun and playing Fallout. Humans in bunkers underground while the elves on the surface try to salvage the environment. When the humans come back up from the bunkers everything is alien and different. The conflict would arise when the elves, created to salvage and protect the fragile environment, are faced with the humans, who of course behave like humans.
* Crashing an alien colony ship into feudal japan could lead to interesting scenarios, especially if you flash forward to modern earth from that point. The results would depend on the type of alien or aliens in the colony and whether or not they remained exclusive to japan or spread out into the rest of the world. Such an event would have an extreme historical impact on the entire world even if the colonists remained where they landed.
* On the previous note why not swap a city on Earth with a city in a parallel reality. You could take that from either perspective or have places that bleed through and form bridges. Anybody controlling a bridge point would have a lot of power.
* Tech that mimics the ancient concept of magic through higgs field manipulation could lead to interesting scenarios depending on who had access to it. Learning to use the system would take special individuals. Messing up would have dire consequences.