Pretty simple idea and not a new one, but imagine hopping on a train at a train station located at the intersection of two interstates or a small city, and relaxing as the train takes you to your destination. That destination could be across the state, or across the country. Routes would be much more direct and accessible than current Amtrak service. This would supplement highway travel, not replace it.
Existing nationwide interstate highway construction consistencies would appear to be a good fit for rail service down either side of the interstate, or possibly in the center median. Bridges could be modified to allow trains to use existing interstate overpasses. Traffic and fuel consumption could be reduced as more folks park their cars for medium and long distance trips.

Off-the-shelf hardware could make this a reality. No technological advances would be needed, just social and political will. There is an organization that is looking a few steps beyond the proposal outlined here, and it is worth looking to see what the future of this type of rail service could evolve into, if acted upon.
http://www.interstatetraveler.us/