I had a Hemi, with 4.56 gears. It got 12 mpg normal driving. Towing 5000 lbs, it got 8.5mpg. The programmer will help you some, maybe 1 0r 2 mpg. If you change gears to help it get up to speed you will hurt the mpg. Because when you are cruising the motor will be turning a higher RPM. You spend more time cruising than accelerating. Air filter and exhaust mods will help you better.
Or you can get a diesel. I traded my hemi for a Power Stroke. Now towing 5000lbs I get 14 mpg under the same conditions. Hwy mileage is about 17 without my programmer and 19.5 with it. When I put the 35's on there I should be over 20 mpg hwy. Because its diesel the larger tires will slow the motor down on the hwy, which is also where the torque happens to be. Not to mention diesel is cheaper right now anyways. All I have done is intake and 4 inch turbo back exhaust(got rid of the kitty too), And an Edge Programmer
Also, I lost 3000 trading in my hemi, but over the next five years, roughly 100,000 miles, the truck is financed for I will save 10,000 in fuel costs.
Diesel Power did a gas vs diesel test, towing, mpg, etc. in last months issue