I had a '96 F350 ext cab, short box (460/e4od, 4.10 gear, 285 tires) back in the day and averaged 9-12 mpg, depending on what I was pulling and speed of course. Mostly it pulled a 2-place aluminum enclosed snowmobile trailer with 2 sleds in it running 75 mph and I swear that it hardly ever had to downshift on the hills. It was a huge improvement over my previous F150 302/5-speed.
I got rid of the 460 truck and replaced it with a '99 F250 ext cab, short box with a V10. I liked the truck, but it didn't have the torque of the 460, and the fuel mileage was slightly worse. Same driver, same snowmobile trailer, etc, and the sucker would have to downshift on the hills. I was pretty disappointed in it overall.
I'd say build yourself a 460 tow rig, I think you'll be happier than you would with a 5.4/6.8 modular motor.