I tow with my 2000 E450, Class C, in Overdrive most of the time on the interstates. Some hills will make it downshift but that's to be expected.
On secondary roads, with hills or traffic lights, I go with Overdrive off.
On local roads I leave it off, just to help with the braking.
If you find it downshifting often, that's when you should turn it off.