The ultimate answer to this is what your term of ownership is and mileage put on. Highway miles are easy, if you're only going to own it for a few years and put a lot of highway miles on, go for the most fuel efficient modern design that will tow (if anything) what you need of it.
If you're in it for the long haul, choose the highest displacement old school design that will tow what you need. You will lose a few MPG and more than gain it back with reduced maintenance and repairs.
If you doubt this, price a low mileage pull or rebuilt 5.0L vs a 3.5 EB, and this is being generous to assume the EB is the newer design where intake valves don't carbon up and need cleaned every 75K mi. or so.
Might be a different conversation if it were a heavier duty than F150 but it is a good, popular vehicle for many uses. Seems like there was a survey or three on youtube a while back where the Ford mechanics that work on these were asked which engine they would choose, and the 5.0L won. If they don't have experience with which engines have more problems, who do you suppose does?