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On my truck my MPG is the best with my race tune from innovative. Since you tow pretty heavy I'd suggest a good tow tune with the jake brake option turned on and then a good economy tune and probably a hot tune for when you wanna have a little fun with it. Contact Eric at Innovative Diesel, he can set you up and you'll have awesome tech support and everything gets delivered quickly.
but with my truck i think it got better mileage with a street tune. if i had a hotter tune and it would always smoke off the start and driving stop go i think that hurt my mpg's a tad (i do have larger injectors though). highway unloaded i think the hotter tune the better but i never really got a chance to do any mpg testing with a race tune on a long trip.
now i am running an innovative xtreme street (haven't check the mpg's) great tune but insane power (way more than expected) i had to email eric and have him turn it down a little bit. (haven't had the chance to try the new tweaked though)
VXCF4 (2005,2006,2007MY)
Stock + 20HP, "tweaked" stock calibration.
Heavy Tow 40HP, Safe to tow Max GVWR of vehicle
Heavy Tow w Engine Brake 40HP, Safe to tow Max GVWR of vehicle, with turbocharger exhaust braking
Aggressive Tow 65HP, Safe to tow/haul 10,000LBS payload
Aggressive Tow w Engine Brake 65HP, Safe to tow/haul 10,000LBS payload, with turbo exhaust braking
General Economy 90HP daily-use economy file, 7500LBS tow/haul limit
Max Economy Designed for maximum fuel economy; no assigned power or tow ratings.
Mild Street Economy 100HP daily-use performance and economy calibration
Aggressive Street Economy 130HP daily-use performance and economy calibration
Hybrid Race 150-170HP (Dependant Upon Calibration) performance calibration
Ultra Competition 175HP Drag-Race/Sled Pull ONLY calibration