Bem-Vinda! Welcome aboard the RoadTrip America Forums!
I am also a fan of renting a guest house rather than staying in anonymous motels. They can be much more relaxing and let you get a bit of the flavor of a neighborhood and the local culture. They can often even be a bargain, especially if you are traveling with a group of more than 2 or 3 very close friends since you can take at least two of your daily meals 'at home' having prepared them in your 'own' kitchen from local foodstuffs rather than eating out every meal. They often come with full laundry facilities, WiFi, excellent entertainment systems, and more quiet than is typical of motels, and the opportunity to simply be alone rather than all cooped up in the same room. But there is a downside. Typically, they rent by the week or longer especially during the local high season. although occasionally you can find owners who will rent by the day (more expensive) if the unit has not been fully booked.
So in your case, depending on what your schedule looks like, look for a house rental (search for 'vacation rental') in a town midway between a couple of your destinations and use that base to explore of those destinations. For example, you could get a rental near Daytona Beach that would be good for both Orlando and St. Augustine, as well as a little beach time. Then take another near Darien GA for use in seeing St. Marys, Savannah, and the Cumberland Island National Seashore.
New Orleans is considerably farther away from the rest of your destinations. So much so that you might want to reconsider why it is on the list. It would be a very long day, over 600 miles from most of them, and would greatly increase the amount of driving you would have to do - and decrease the amount of time you have to explore the rest of the towns and cities on your list.
AZBuck