My experience is that automatics suck about 2 mpg off the top. My understanding is that automatics work better at high engine rpm which provides better hydraulic pressure, but the best mileage is at lower rpm where you rely on engine torque. With a manual transmission, I consistently get 2 mpg better than anyone I know with an auto in the same truck.

Cue the Sammy Hagar music.... :-)

Seriously, though, this is a very badly overlooked and/or misunderstood point. In a discussion elsewhere someone tried to point out that it equals out because your engine runs longer; he had completely missed the point that MPG (and its metric counterparts) lack any reference to time at all. More MPG is more MPG, period.

A few years back, before all of the massive shift in gas prices, I took a trip across New York State in a car that was not particularly fuel efficient. It was rated 22/32 MPG (a 1998 Subaru Impreza waggon), and my typical commuting fuel economy was actually only 18 MPG. Driving it across the state on either US Route 20 or NY Route 5, however, it got 34 MPG. Most of this travel was at less than 55 MPH.

I would also point out that these back highways can be far more interesting places to drive than the Interstates. By all means, use the Interstate if you are in a hurry, but if not, take your time and enjoy the trip.