I have been told that the lower geared, bigger tired F-150 really suffers on gas mileage around town and towing.
I commute daily 18 miles each way and usually add 6-12 miles a day if I go out to lunch or have a client appointment and avg 17 mpg between gas stops. I've got the 3.73's and 20" wheels.. I'm mostly in rush hour traffic and avg maybe 30 mph over a 2 week period.
I just did a 210 mile straight hwy run to Sequim from Puyallup WA and back where my folks live and got a solid 22 mpg on the computer.. Yes, I know everyone says the computer is always wrong, but mine is pretty darn close and I'm rounding DOWN anyway... ;)
A lot will depend on how your drive it too of course.. Keep in those turbos and it'll suck the gas! I do get into those turbos a bit too, but I can also drive like Grandpa too... :)
I think I get better mpg with the 3.73's on my commute because of how slow my avg mph end up being.. Anyway, it's all speculative and get what you feel will work best for you and go from there... Folks are happy with 3.15 geared trucks, so there you go! :)
Mitch