I dunno, actually. Given that cruising is very efficient compared to stopping and starting, I think if you decided to optimize for fuel economy at exactly 100mph you could probably squeeze that kind of fuel economy out of a car. Optimize for aerodynamics, give it a tiny cross section (I'm thinking passenger behind driver), lowest rolling resistance tires you can manage, and put in a small engine and a super-long gearbox so that your engine is turning at maximimal efficiency when the car's doing 100mph. I don't think it'd be that difficult. On the downside it would of course be tiny and have terrible acceleration.

Or, to put it another way, my big heavy car gets nearly 30mpg when cruising at 100mph, so all you really gotta do is reduce drag.