Traveled US-50 and US-60 from Rockies to East Coast, but only sections of US-40, about Mississippi to Appalachians (western Pennsylvania). I've also taken US-30 and US-36 into western Pennsylvania.
To me, it is worthwhile for local flavor and scenery, and yes there are small towns to slow down for; that is the local flavor. Hills only where there are hills. To get to the East Coast you have to cross the Appalachians, those are mountains, not hills.
Definitely slow in places, as the US numbered highways are used heavily by regional trucking, because the Interstates do not go everywhere and are limited access. On US numbered highways, the traffic mix often includes large slow-moving agricultural equipment, oil field equipment, manufactured homes, wind generator parts, and animal-drawn vehicles. If local traffic slowing you down bothers you, stick to the Interstates. That big slow stuff is not allowed on the Interstates.
If you want to travel the US numbered highways, double the travel time in your trip planning, to cover slow sections and stopping to see things.
Pulling a TT across the Appalachian Mountains, I would use the Interstate system. It is about having enough traffic lanes to not be holding up faster traffic and being slowed by slower traffic.
Tom Test
Itasca Spirit 29B