Between the "highway gears", the AOD's deep overdrive, and the larger tires you may get better mileage, but get to 60 sometime within 10 minutes. The 300 is a torquey motor, but that's asking quite a bit. Don't even think about hauling.
Lugging around with the pedal floored will not save any gas versus an easy cruise at a higher RPM. It will also put a lot more wear and tear on the motor from the constant max load. Even the slightest incline would cause a downshift since the motor would immediately bog down, bringing your revs up.
My old truck with a 300 and a 5-speed and 3.08 gears would average around 16mpg straight highway, closer to 9 or 10 around town. That manual had a .8:1 overdrive gear. It didn't have a tach, but I'd guess revs were somewhere around 2200 or so at highway speeds.
I doubt you would get much of a MPG increase with the swap. You're trading revs(hp) for "lug"(torque).
If you're looking to get a more fuel efficient vehicle, either look into a newer used truck possibly with the 4.6 or if you need a commuter some used econobox just to run to work and back. You can swap and tune one of those trucks all day long, but you're never going to get good mileage. They're big trucks with big motors, sucking gas comes with the territory.