My reason for NOT using cruise (Ford F350 6.4 diesel towing fifth-wheel) is transmission wants to downshift on slight upgrade. I find that I use less fuel by building up speed (using as little throttle as possible) before slight upgrades, letting speed drop on upgrade, then building up speed on downgrade. The idea is to avoid too many downshifts.
Even on flat-as-pancake Florida interstates, my truck tries to downshift when going up an overpass. As an experiment, I tried 100 miles with cruise on, then 100 miles with cruise off. MPG improved from 9.0 to 10.1. In hilly country, the difference is greater.