Adding a few others I don’t think have been mentioned yet:
-if you take 81, stop at Natural Bridge in Virginia. It can be done in a short amount of time but there is also a little cafe in the visitor area so it’s a good way to break up the drive.
-Abingdon, VA is a cute town with good access to hiking trails and an historic theater that is a good spot to catch a play if you need an overnight stop.
-if you take the 65/71 route instead, Bernheim Forest just outside of Louisville is my favorite place to stop. You can do it quickly but could also spend a full afternoon quite easily too.