Briefly, I don't think renting a Hybrid for a road trip will be worth the extra cost if you're only looking at saving gas. At EWR for example, the Prius is going for almost double the price of regular midsize cars for a weekly rental.

I've rented Prius about a total of 4 week over the last couple years. Without changing my driving style I get about 45 MPG combined, but mostly highway. That's the indicated MPG on the display. Not sure of the actual calculated amount.

I can get close to 40 on a Corolla or my parents Honda Civics (96 and 2005 Coupe EX).

I also drove a Lexus RX400H for a day and got mid-20s MPG, about the same as the Highlander Hybrid (they're basically the same car). Considering our V8 Infiniti FX45 gets about 20 on the highway, I don't consider 20's a great achievement.

Also as another data point, we rented a Corvette in Florida and got 30mpg on the highway. I bet it could be even better if I drove the posted limit.

For comparison, in NYC traficc we really saw the advantage of hybrids. The Prius got us about the same 45mpg, but our Infiniti only gets around 9mpg, our MB SLK350 gets about 17mpg, MB C300 loaner also got around 17mpg.