This might work for you. I travel Us 23 all the way to Kingsport towing my 5th wheel. It may be 30 minutes longer than going to Lexington from Huntington and then traveling I-75 south but it's something differnt. I like to go somewhere one way and then return another way....don't enjoy the same scene twice. If you like making the journey part of the fun then try it.
US 23 is a 4 lane great highway but does have a few red lights along the way. No big deal, just from time to time you have to stop. I've never counted them but it's not an issue! There are no intersections you turn on or towns to try to get through. On the other hand if you are the type of traveler who hates the journey, won't stop unless you are out of gas or need a restroom, cannot wait to get there and then brag about how many hours it took you to drive it, maybe following the Interstate is your best bet. Interstates are rarely patrolled anymore and people get away with 75 to 80 mph all the time. Of course one major mistake by another driver can close an Interstate for several hours. This cancels your advantage of Interstate travel.
I would not hesitate to try this route at least once. It's all 4 lane and you see something different. Go down one way and come back another. Time it so you can tell us later! By traveling to Cincinnati it looks like to me you are going out of your way.
Many people from Huntington go to the Smoky mts by using US 23!