We have gone from ND to SC and back 3 times in the last 5 years and have taken three different routes to add States to our map of course.
Things we learned:
Depending where you are at in NC, I-77 through Wytheville, VA to Charleston, WV, then over the mountains on I-64 to Lexington was way easier than climbing the mountain at Asheville, NC on I-40. Yes, there are some tolls but grades were lighter and some curves but...
Indianapolis, IN to Davenport, IA on I-74 kept us out of the Chicago area and was a nice pull. Don't forget to stop at the Iowa 80 truckstop west of Davenport. I-80 all the way to the north side of Omaha, then north on I-29.
I-90 is a pretty boring drive but just picture the movie "Dances with Wolves".