It is too early to predict Covid numbers in late March. My wife and I need to be careful too, and have paid out for cancellations when things were bad. (Not what you want to hear...) We have taken several trips without problems, and I am guessing FL will have burned through Omicron. (Don't tell the virus that March 14 is Pi Day!!!)
The lowlands of SC and Georgia offer plenty of state park accommodations, including many with historical interest. Get on their park websites; then double check the ratings on Campendium or a similar resource.
Charleston has much to offer, but is not "off the beaten path". There's Patriot's Point (the Naval Museum), Charlestowne Landing, Pinckley Historical site, either Magnolia Plantation or Middleton Place for a garden (call to check on what's blooming and avoid peak tourist days).
If you spend time on an island (like Jekyll or Amelia), or St. Joes on the panhandle, bring insect repellent if the mosquitoes or no-see-ums are expected to be out. As BSWG mentioned, Florabama is a nice alternative, but can be crowded.
Skidaway near Savannah is a nice RV park and convenient to attractions there. We find that city to be a bit more "precious" than Charleston, but it has a lot to offer, including day trips to historical sites further out from the city.
Florida is great, but beaches tend to be crowded especially on the Gulf side. Avoid Daytona around Bike Week! Parks like Anastasia and Gamble Rogers are nice for beach time, but tough to book. St Augustine is a very nice historical city, but was heavily visited the last time we stopped there.
Consider county parks and COE's for your stays, for better availability.
On I95, the first mile marker is 383. That's the distance to Miami. Key West is an additional 140 miles further. Mid-state, around mile 220, Merritt Island and several water reclamation sites are good for bird viewing (best EARLY in the day). M.I. is close to the space center - call ahead if you have an interest in that to avoid launch closures. On our first visit to FL, we thought the best bet to see alligators was the Everglades. (That was the year of the December government closing, so that park was closed anyway.) We saw more at M.I.
My final thought is, Don't exhaust yourself on the drive down. Twenty five years ago, we had two kids, a twelve person van, and much more youthful bladders, so we would drive from Chicago to Gulf Shores in two days to make the most of a ten day spring break. What were we thinking? There are a lot of pleasant "recovery day" attractions along the way.
(That man in that tiny can)
(Same man, Bigger can)