Unless you tow heavy loads more than once a month, or tow mountain roads fast (interstate highways) then the 5.4 will be more than enough.
The mileage from my F150 SuperCrew, 4x4 & 5.4, is ~14 mpg around town, with 3.55's and 285/75's. The lack of low overall gear ratio makes it sluggish for drag light starts but it pulls hills fine. I test drove it for a tank with the overdrive off, to test the mileage with a better final gear ratio, and the mileage stayed the same. Even with the poor tire and gear combination it does not run out of power towing my fathers 21 foot flatbed trailer (with 8000 pounds of tractor, trailer, and impliments), but the mileage drops to ~11 mpg with the load and wind drag.
The F250 SD helps the 5.4, as it opens up the 4.10 and 4.30 ratio options that are not available with the F150. The gearing helps the 5.4 SD tow loads without killing the mileage (something I would have considered to upsize, if I had known how the engines deliver power and mileage). I have heard the 3-valve 5.4 heads help the mileage, and still like to rev.
The mileage trade off with towing gears is the difference with the 6.8, as my father has a 29 foot motorhome with the V10 and 4.10's, and it gets 10 mpg unloaded and 7 mpg towing the same trailer load as my F150. Both modular engines like to rev, but the rpm hurts the 6.8 mileage more than the 5.4. The 6.8 never runs out of power (if you foot the throttle) but the mileage is no better than my fathers old C900 with the 538 when you are in a hurry.
Just to toss out other data points my father's 7.3L Surburban (454, 4.10) never gets better than 11 mpg, and delivers ~9 mpg towing the same loaded trailer noted above. The new 6.0L vortec's at work deliver about 16 mpg unloaded (better than the Ford 5.4) and the 5.3's deliver nearly 20 mpg unloaded. Good mileage is where the Ford engines fail to match the Chevy's, although they close the mileage gap as you load the engines with trailers and weight (some of our 5.3L service body trucks are getting only 10 mpg with the excess weight they carry).