Can you please tell us-
What time of year?
How many days to make the drive?
Are you driving back to Charleston? Do you live in Charleston? As you may have been to all the places nearby I mention.
Interest? Hiking? Nature? Art? History? Civil War? Partying? Food? Landscapes?
Poster #1-
I would NOT call Indianapolis, Louisville, Charlotte pretty. Lexington and horse country, or the Bourbon trail is nice, as is the Asheville area. Pretty, would be Charleston, Savannah.
It all depends how many days you have to drive it, and your interest.
I make this drive all the time, both in a car and on a motorcycle, but from Chicago to Charleston.
The nicest areas and best thing to see and do in Smokey Mountain National Park, and the Blue Ridge Parkway. This needs 2-3 days alone. SMNP is the most visited National Park in the US. Second would be the Asheville area.
But we normally stop first in a area between Louisville and Lexington, Shaker Village, which is a nice estate near Harrodsburg and Danville, two old Kentucky towns of historic interest. The Bourbon Trail is also in Bardstown.
https://shakervillageky.org/
We then usually head down to Cumberland Falls KY, this is a nice state park, great hiking, rafting and camping. They also have a MOONBOW, which when a full moon is out over the waterfalls as night, its gorgeous.
https://parks.ky.gov/parks/resortparks/cumberland-falls/
Nearby you have Berea, and lots of small interesting Bluegrass towns, roads and scenery.
Then we head from there to Gatlinburg Area, and into the SMNP, and drive 441 thru the park to Cherokee, and stay there 1-2 nights, or, over in Bryson City. (hiking,rafting)
The other option is to head to Asheville area on the Blue Ridge Parkway, and either stay in Asheville area, or, rent a AirBNB Cabin near Asheville and in the foothills above, south west of town, tons of great places, great hiking and great driving. Nearby you have Brevard, Highlands and Blowing Rock/Hot Springs. You can spend a week in this area if you want.
Asheville you have the gorgeous Biltmore Estate, great art and music scene, and good foodie scene.
https://www.nps.gov/grsm/index.htm
https://www.biltmore.com/
https://www.exploreasheville.com
From here, we usually stop a night in Greenville SC, which is a very cool downtown and foodie scene. Then we head to Charleston.
Charleston is one of the prettiest old American cities, and the historic area is just dripping with history, as well a great old homes and historic district, as well as the plantations nearby are a must. Allow 4 nights in Charleston, a week is best. Hotels are not cheap, its a huge wedding destination too. $300 night is normal, if you want to walk everywhere, as car in Charleston is not needed and expensive to park. If hotels are too much $, consider Mt Pleasant area right across bridge....
Side trip for areas of interest, are Madison Indiana on the Ohio River, NOLA area of Louisville KY, Lake Fontana near SMNP, Tellico Plains and drive the Cherohala parkway, the backway to Bryson City/Cherokkee, base there, then drive 441 North and back as a day trip, its a gorgeous road thru the park, but weekends and July/Aug is crowded.
https://cherohala.com/
Lots of great hiking, waterfalls, rafting, camping and nature in KY & NC...