Best you can do is try to keep the wind at your back and your speed under 65 MPH. Air drag increase is the square of the change in velocity so driving 20% faster increases air drag by 44% and will drop your MPG accordingly.
There is something also to be said for avoiding routes that require a lot of elevation changes where you gain elevation and then go down and then have to go up again as there is extra work involved for the engine which takes more fuel. The truck routes usually are in the less scenic areas where the terrain is flatter and fuel economy is better. Just need to decide whether it is worth it or not.
Even so the best you can probably due is a 15% improvement and so instead of burning 120 gallons of fuel to go 1000 miles and spending $500 you burn 102 gallons and spend $425 to go 1000 miles. I would rather pay the extra $75 to go the scenic route.