A F-250/350 with a 460 is not a daily driver............Its a piece of heavy equipment. Do not expect to make the mpg bearable for such duty, its just not going to happen.
Consider a Kia to drive when you don't need the truck.
The only thing I have found that helped even very slightly was going to long tube headers, took me from 11.5 to 12.5.........that is after I quit exploring the new found performance bump.
I put in a throttle body spacer, did a shorty exhaust, keep well tuned, have replaced a lot of 27 year old sensors, injectors, dizzy, cap, wires proper copper plugs. Regular additives, seafoam, throttle cleaning, oil and gear case changes and run 93 oct.Tires 75# / 65#. Mileage typical between 12(stop&go) - 14 longer trips. I have a cab height cap, which helps.