Better mileage than average new passenger vehicle in 2.5ton commercial truck!
Drive very, very, very slowly, and you can get 25mpg on diesel while using the truck as a truck.
Most of the suggestions made regarding Project Groovy apply here, but they all cost money, which you won't have if you commute in an F250.
Is there any hope, you ask? Yes, there is hope for saving lots of fuel through ecomodding. Driving style and simple mods will save you more gas than I burn in my Insight. But no, there is no hope for having a truck that uses as little gas as a car. The laws of physics prevent that.