1 week in the Southern U.S. Where to go? How to get around?

Doing a combination of Charleston and Savannah should be on the very top of your list.  Both incredible places with tons of history and extremely Southern.  They have everything a visitor could ask for.  You could spend a lot of time in both, but even 1 or 2 nights are worth it.  

In fact, I would go so far to say that it would be a travesty if you went to Atlanta and didn't visit these two places.  

There have been some great recommendations here, but I'd like to address how to get around. Truthfully, renting a car is the best way to see everything, but drives are long and renting is expensive. Amtrak is also expensive, but only goes so far. I'd recommend taking Megabus as much as possible, as it goes nearly everywhere you want. Plus the tickets start at $1 and have comfortable seats and bathrooms on board. Also check out Southeastern Stages and Greyhound as backup options. Happy travels!

I would suggest a few days in Atlanta, where there are a lot of great restaurants (from Varasano's Pizzeria to Bacchanalia).  If you're into food, I can give you many more suggestions. And yes, I think a car is a necessity.  Atlanta highlights: Atlanta Botanical Garden, High Museum of Art, and head north a little to Marietta Square.  

About 4 hours drive Northeast is Asheville, a fun town with many restaurants and shops.  Most people in Asheville are foodies, and the restaurants reflect this high standard.  The town itself is great to visit, but what's even better is seeing the Biltmore Estate.  

This is the largest residence in the US, built in approximately 1900.  I could spend a week just on the Biltmore Estate nestled in the beautiful Blue Ridge Mountains.

Enjoy your trip!

In Georgia:

• Atlanta is the largest city in GA with the most to do; from theme parks, to bars and everything in between.
  
• Athens (Georgia) is a college town near Atlanta, if you're a Bulldog fan then check it out.
• Savannah is a coastal city that has a lot to do and is a lot of fun.
  

In Florida:
Jacksonville is my favorite but Daytona Beach and St Augustine are two very touristy areas.

You will need a car, most places have poor public transportation.

On a side note, i've heard that both Gatlinburg and Chattanooga are fun.

Depending on where you want to start and if you want to be as far South as a coastal trip.....You could start in Houston, TX or near there (Austin, the Hill Country) and travel across Louisiana, Mississippi, Alabama, Georgia (State), to Florida. Austin is a quirky town with lots of music, art, and night life.  Houston has a quite a bit to see and do.  Louisiana has some excellent Cajun restaurants and New Orleans French Quarter is always fun with live music.  Mississippi has casinos and some great fishing. Alabama has some beautiful beaches, Dauphin Island is not far off the highway and is a great place to relax and unwind. Georgia has beautiful plantations you can visit. Last but not least Florida is, what can I say?  Most of it is beautiful. Pensacola, Destin, so many beautiful places to name. It is about a 9 hour drive from Houston to Pensacola FL if you drive straight through. If you have a week to travel you could take a day here or there to explore on your way.  If you do go coastal be sure to take a map of the lighthouses in the areas, there are several along this trek. 

The South is a great place to travel.  My personal recommendation is by car.  Buses are an option but most southern cities don't have good public transportation and things are very spread out down here.  As an example, if your in Atlanta and want to see Stone Mountain the only way to get there is in a car.  

If you decide to do a coastal trip, I would suggest starting in Atlanta and then driving southeast to Savannah, their is a lot to see and do there.  Next I would go to Charleston which is, IMHO, the jewel of the south.  There are lots of little towns along the coast that you might like to see but one of my favorites is BBeaufort.  From there you might consider going to Virginia Beach or Washington, DC.  I'm afraid that I don't know the Virginia area very well so I won't comment too much.

Please be aware that the South gets very hot in the summer time.  We've had a good mild one this year, but some days will leave the locals not wanting to be outside let alone people not accustomed to it.  Late April and early May tend to be our better months.  Traditionally, I look towards Memorial Day as the time when we get unbearably hot.  

Many people that are not accustomed to it, find driving in Atlanta to be a nerve racking experience.  Expect people to be driving 75 to 85 miles an hour and changing lanes frequently. If that concerns you, I would recommend traveling the freeways during non rush hour times.  Outside of the greater Atlanta area, it should be normal.  

Hope you enjoy yourself. Let me know if I can be of further information.  

Atlanta is a good jumping off point for a couple of reasons including its size, central location and ease of getting in and out through the airport.

Lots of cool stuff is not far from Atl but you'll need to rent a car to see them. They include Savannah(about 4 hrs away), Chattanooga (about 2.5 hrs away), Birmingham (Alabama) (2 hrs away) and Asheville and other parts of western NC (about 3 hrs away)

If you are a beach lover than the Florida and Alabama gulf side/panhandle beaches are much nicer than GA or the Carollinas but they are all alot of fun. Enjoy.

You'll defiantly need a car. The amtrak does go from atlanta through the Carolina's up to virginia but if you were to from Atlanta to Myrtle Beach, best to take a car. The train doesn't have a direct route and it would be out of the way. 

Martin Luther King Jr. National Historic Site and Jimmy Carter Library and Museum are two places not to be missed. City Pass is an excellent deal for places to see also. The Varsity is great for the atmosphere. Flying Biscuit Cafehas a great breakfast. Piedmont Park is Atlanta's Central Park designed by the same architect. Rental car is the fastest way to get where you need to go. Be sure to pick up the tourist books at the travelers aid desk in the airport. Say hi to Kenyi who works the desk. No Mas! Hacienda & Cantinahas great mexican food and gifts. Mae's Bakerywas recommended but I'm off sweets these days so I haven't been there. Stop by Lenox Square Mallone of the oldest in ATL with quite a face lift! Fat Matt's Rib Shack has excellent ribs and music. Small but good food. That should keep you busy for a few days. Start south and work your way north to the Carolinas, enjoy the sunny south and the great hospitality.

In the south, a car is necessary to get around.  As far as beaches, I would avoid myrtle beach, and spend some time in Charleston instead.  Isle of Palms has great beaches, there is a great brewery (Westbrook Brewing Company) and Charleston has some awesome shops and things to do.  

For a week long vacation you could fly into Atlanta for a couple of days, drive up to Charleston (about 5 hours) for a couple of days including some beach time, and then head to Asheville, a cool town with lots to do.

Hope it helps