While i dont know if this is family trip or your interests, here is what i would look for
I am assuming round trip and i would go different ways and am including nothing in Texas as that can be done at any time
First would be Northern route
Stop at President Clinton's library in Little Rock...impressive
Drive to Memphis...check out Peabody hotel for duck march, Flight for a good meal and carry on on Beale Street to live music....they have a good zoo if you have kids and Corky's was good for BBQ. next day hit up Graceland before leaving
Nashville continues your journey with Country Music Hall of Fane and a backstage tour of the Ryman.
I am then partial to going to Kentucky and seeing Manmouth Caves, Louisville Slugger facility, and Churchill Downs race track
Try then to hit up the skyline drive until you reach Virginia area east of Charlotteville, or maybe the Blue Ridge Parkway although i think the more scenic portions are futher south on the road
While a slight detour back hitting Asheville would be amazing with breweries and hiking in and around Blowing Rock. This would allow you to hit up the bettr parts of the Blue Ridge Parkway.
Return trip
Get to the coast from Charlotteville in time to hit up Colonial Williamsburg, an the amusement parks in that are before heading to the Outer Banks of the eastern portion of North Carolina,
Travel down the coastal area and spend a couple of days in Charleston and then Savannah with a stop in Beaufort SC. Hit up one of the islands either San Simeon, Jeckyl or Cumberland in that general area.
If you want to see Georgia then Athens is a great place along with Macon, Augusta for smaller towns and if in the area on a sunday President Carter still holds Sunday School classes to the public in Plains Ga. Atlanta has some exciting things to do but traffic is a complete pain.
Drive to New Orleans and then after a couple of days of exploration hit uo Laura Plantation or Oak Alley before your drive back to San Antonio
So many things to do and see that are historical as well as foodie places and pleanty options for kids if in tow
***get your tickets to Monticello before arriving because they were sold out the day we were there and only hit up the outside area and some others. Also a stop in Mount Vernon and Madison's home while in that northern area of Virginia is a must