I ran my 71 F100 for years as a daily driver, .030 390, 9:1, 270H, Street Dominator, 600 Holley, headers, recurved distributor, 4 speed, 4x4, 3.70 gears, 33 inch tall tires. Ran at 12.5 around town and 14.5 on a long run, ran great but wasn't knife-edge tuned back in the day.
As Frank said lots of inputs, but, keep overlap low, compression high, mixture on the lean side for mileage. Tight quench helps the the lean mixture not ping, and then it's all how you drive it
My Mustang (4.89 EFI 4.11, TKO-600) gets about 15 on a good Nebraska back road trip, but I also tend to horse it now and then. It does well due to the gearing and EFI, certainly not built for mileage