Hi. Happy to help.
In the past, we have driven 422 to 202 to 95 to I4 in Florida. It's worked very well, BUT last August we got hung up on 95 from Washington DC to Richmond VA. It should have taken 2 hours, it took closer to 7 with a lunch break. Awful! We kept that route in February because there's no beach traffic and it was great.
So, this summer we're going to try the 81-77-26-95 way. Depending on when we leave, we'll either go through Lancaster or up towards Reading/222/Harrisburg. Technically we'll go the same way once we hit Harrisburg, though.
We expect to take around 12 hours to Walterboro, although we may stop in Columbia SC if we're tired, or Orangeburg. We have no idea what the drive will be up to that point, so we'll play it by ear.
Our first couple of drives were right around 2 weeks, driving on the weekends. But we kind of felt it was a little long the second time we did it, so now we do Sunday to Saturday and it works out fine. We know what we like, only make a couple of meal reservations and have plenty of time. We don't want to burn out on the same things over and over so we find that 6 days is perfect now.
They key is always be positive about the driving part. Enjoy the time together, listen to some music you haven't heard in a while, actually TALK to each other. It's amazing how much DH and I can reconnect on things when we have a couple hours to just talk.

That NEVER happens in our everyday life!
For us, we're not wasting that time. It's positive family time.
Let me know if I can help with anything else.