Yah, this can make an overwhelming difference in the long run. I used to drive semi-regularly between Wisconsin and Minnesota, a stretch of about 280 miles; others in my family would make the same trip with the same car during the same times of year, and my mileage per tank was always significantly different, and we couldn't figure out why initially.
Turns out they used cruise control for most of the stretch, which I never used, and it was often the difference of 3-5 gallons over the course of the trip. Not a huge deal, but $4 gas did influence it a bit.
My 2007 Civic doesn't account for incline when doing cruise control. It has some sort of lookup table that says, "When the owner sets me to 65 miles per hour, I go at this RPM." If I keep slowing down because I'm on a hill, it downshifts a gear and accelerates hard until the car goes back up to 65 miles per hour. Wash, rinse, repeat. I always disabled cruise control on hills because of it.
My fiancee's 2014 Nissan Rogue accounts for hills with cruise control, and it never has these intervals.
I find that the cruise control on a 2015 Hyundai (automatic transmission) always gets better mileage than I can without, even on hilly trips. (Where I live all trips are hilly.) I do help it out by shifting to neutral when on long downhill stretches.
Turns out they used cruise control for most of the stretch, which I never used, and it was often the difference of 3-5 gallons over the course of the trip. Not a huge deal, but $4 gas did influence it a bit.