Since you posted about an old truck, I have a 68 Ford F-100 that I poked a stock Lincoln Towncar roller-cam 5.0 in it (302) w/edelbrock alum street perf intake, factory elec ign., factory header type exhaust, still has C-6 (Fords older heavy duty auto) and 9 inch rear was changed to 3.23 pegleg and has Edelbrock 450 or 500 cfm (can't recall right now) 4 barrel. nursing a tank on the primaries and not doing over 60 it gets 14.8 mpg. My daily driver 2000 model F150 w/smaller V-6 and 5 speed manual (w/overdrive) gets 18 under similar conditions. I think in both cases, engine CID is just too small to pull weight. I came real close on the old 68 to poking a 351Windsor in it, instead of the 302, but the 5.0 was much cheaper (very plentiful in wrecking yards), I really think in both cases, my daily driver Ford trucks would have gotten better mileage with a larger/torquier engine.
I also used to have a 66 Impala 2 door hardtop w/282 and 2 barrel, all stock, and it got about 14 (powerglide) on highway. I think a 327 w/4 barrel would have gotten better. I once had a Ford Galaxy conv w/429 and 3 speed auto (C-6) and it got easy 15-17 running the heck out of it and had plenty of power and torque. So, I think you can go too small for the weight of a car and hurt economy no matter how much you light throttle it. Witness all the old stock GM and Ford trucks w/straight 6s and 3 on the columns and no power options (work trucks) that got around 12-14 on highway at most, I know I had 2 of those.
