I drive an early 99 F250 extended cab, just drove from Fairbanks Alaska to St. Paul Minnesota for a grand total of 7500 miles in 2 weeks. See my mods in signature, note I had about 1000 lbs of gear aboard too, plus 2 people. This trip gave me a great opportunity to calculate my mpgs carefully with good statistical sampling!
Also, I run synthetic oil, and add diesel kleen with every fill up. I run sea-foam in the tank about once every 2 to 3 months.
In DP tuner 80hp econo on way down I got over 18.2 as long as the speed was under 65mph. This was true for everywhere I went including the mountains except for North Dakota where I was driving 75 pretty much the whole time, mpg went down to 15.5 ish for that tank. Note that I was not slowing down much when going up hills, and often was having fun accelerating uphill just for the fun of it, so I could have gotten better than the 18.2
On the way back I was hauling a double axle trailer (U-hauls 12x6 if you are familiar with em) and I went through Jasper park in canada, basically up down, up down, up down. I never got under 15.25 mpg and I was towing at about 55-65 the whole time. Note I was running the 80hp tow tune for most of my trip, with a few times of 40hp tow just because it ran cooler in the 7000 ft range in canada. Seems the best fuel economy is under 600°F on the EGTs and under 5-7ish PSI on the boost.
My last mod is called leaky intercooler boot mod -- drove the whole way down and back unable to make more than 20psi of boost, fixed it the week I got back, now I can get around 24psi again, still think I have a small leak but have to wait to buy new boots for the intakes.
Bottom line, the air drag is what gets ya ... keep it under 65 and you will love your fuel economy with just a few mods... I am still planning on getting a 4" turbo back exhaust with higher flow muffler, so once that is done hope to see a tiny bit better... I wasn't being a granny on the acceleration for most of the trip and I still saw these numbers...
Hope this helps...