Interstates were built to serve the needs of the trucking industry (and represent a subsidy of billions of dollars if not trillions of dollars) and they will always be the straightest and flattest route you can take. The downside is that it will also have the most trucking traffic on it as well so often the decrease in total distance is offset in large part by traffic moving at a slower pace.
If you burn diesel the interstates is where you will find most of the stations and truck stops for both diesel and DEF and the worst restaurants.