BTDT. 06 Frontier towing a 4050 lb TT. Similar config (2wd) with 6500 tow rating. MPG's were abysmal to say the least. After a few months of towing I traded it in on a used 08 F150 5.4 3.73 gears. Mpg's went from the 8-9 range to a solid 10.5+. The F150 barely knew it was back there. Nicest thing was I jumped to a 26 (?) gal tank which bumped my towing range to 200 before looking for gas. I had a Scab and 6.5 bed which also made hauling camp gear nicer.
By far the least cost effective measure is replacing the OEM tank. The upside to a larger truck is more room and the possibility of up-sizing the TT. I would look for a used 1/2 ton or even a GM midsize diesel.
