I had an 88 F250 4x4 with the 351, C6, 3.55 axle and 33" tires. Fuel mileage went from Bad to Worse. Got about 16 hwy and 12 city. I miss that truck!
At the time, I had a friend with the same truck with the 460 and his mileage was about 16 hwy and 10 city; so if I did it again, I would get the 460.
Best improvement: Thorley Headers and dual exhaust.