When I headed back east to grad school many decades ago in a pickup with a small TC (but not towing), I decided to take the scenic route. Probably added 1000 miles to my trip, but less than 50 miles out of 2500 were on interstate, the rest on US and state highways. No doubt it added much time to my trip, but one has a better chance to see the local "color", eat at out-of-the-way restaurants, and interact with locals one wouldn't meet cruising down an interstate.
Today, while we may use interstates to get the first 500 or 1000 miles under our belts on longer trips, we get on the smaller roads once we're past that point. In many ways, that's when our vacation really begins.
If you have the time to do it, by all means stick to the US and state highways for the most interesting experiences.