It's a mix for me. Personally, I prefer the "blue" highways most of the time, however sometimes the interstate makes more sense.
On our cross country trip in 2014 from Virginia to LA, California I would guess the mileage split was maybe 55% "blue" and 45% interstate.
Generally speaking, the pace is slower on the "blue" highways which suits me when pulling the trailer, and the scenery is generally better from other than interstates.
However, there is one state I personally know about that it's always advisable to use the interstates, and that's West Virginia. A couple of years ago I made the mistake of taking US50 across WV rather than I64. One of the worst decisions I've made driving. Never seen so many hairpin type curves and 9% grades going up, and obviously doing down.
Unfortunately, or fortunately, I do all the driving.
