I have several 6.2l F350's & one F250.
The 350's are work trucks, 185,000 ~ 344,000 miles.
All have had carrier bearings & u joint replacement, 2 had front wheel bearing replacement, 2 have had alternators, 2 others water pumps & thermostats, 1 radiator, 1 a/c compressor dryer & condenser & hoses, 1 had the rear end rebuilt the rest just routine maintenance & normal wear items.
Of course the one with the highest miles has had the most work, bought it used with no maintenance records.
2 I bought used, 3 new - 6.2l fleet average mpg = 10.18.
The F250 is my daily driver, all miles & driving conditions combined mpg = 13.58.
6.2l / 4:30
Hauls all sorts of stuff & pulls gooseneck with all sorts of stuff tractor, hay, livestock frequently.
Nothing other than routine maintenance & wear items.
The 3:73 ratio will get better mpg empty/lightly loaded, but you give up a very noticeable amount of towing/hauling ability.
With 4:30's the faster you go past 65mph the mpg will suffer, but they pull / haul great.
Cab, Bed & overall configuration all make a difference, best to review the ---> Ford towing gude