I've had a factory 352, slightly modified 390, and now a 482 all in the same truck with same gears and having driven the same 170 mile round trip many times with each. All three were/are around 13 mph when driven the same way (ie with a light foot) on this round trip.
Factors I believe improved mpg despite the increase in cubes across the three FE's I've run: intake choice, headers, compression ratio, rings, and roller cam (allows use of modern oil).
Surprisingly, adding a gear vendor overdrive behind the 482 had a fairly small (if any) effect.
IMO, in town and heavy footed driving hurts mpg more on a big cube engine than on a much smaller engine.