My brother and I do this a lot. We only pack what we need and take direct flights to large cities. We don't rent cars, stay at hotels, we basically stay up for 48 hours and do stuff.
Sleep on the plane. If you need a nap go to some stupid ass movie and get some shut eye. We only do this is the summer. Hit baseball games, shows, and historical sights.
My wife will never do it, but we basically cram a 4 day trip into 2 days.
A lot of fun, but can be stressful at time. Especially late at night in a city like New York.