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My family and I have been going down to Charleston during Thanksgiving for the past 9-10 years. It's our "get away from the rest of the family" trip. It's a great eating town. Some of our faves (all are links):

Hank's Seafood Restaurtant
Magnolia's
S.N.O.B.

Since I have lived in Charleston for 9 years now, I can tell you the best places to go to and the places to avoid.

How about the avoid places first.

Hyman's - probably the most overrated restaurant in South Carolina. The food is good but not that good. There is always a wait there. In fact, I know that they make it such that there is always a wait there. Locals simply don't eat there. There have been rumors for a long time there was a keychain you could show if you were a local and supposedly you would get in faster.

Jestine's - again it is good food but there are so many other places that are better. Bourdain ate there too and liked it but it is so overhyped it just isn't worth the hassle.

The Wreck - this is a restaurant in Mt. Pleasant. It used to be basically locals only (in fact if you would call them, they would only give you vague directions about how to get there. You basically had to "know somebody" to get there.) Now, it is overpriced fried seafood and a tourist trap. Once it starting getting publicity in Southern Living, few locals eat there anymore. My parents always want to go there when they visit but my wife and I always try to convince them otherwise.

Now for the good places.

SNOB - fantastic!

Magnolia's is good but I much prefer High Cotton (which is conveniently located across the street from SNOB) High Cotton is lowcountry food with a twist. It is definitely one of my top three favs in Chas.

If you like French food, La Fourchette is fantastic. 39 Rue de Jean (which is just around the corner from La Fourchette) is good too but for a French brasserie, it really bothers me that they serve sushi! La Fourchette is a classic bistro. It is tiny, loud and the food is simply amazing. Their pommes frites are the best in the city because they use the almighty duck fat to fry the fries in.

Coast is right next to 39 Rue de Jean and is a great seafood place. Hank's is good too but I like Coast better. I highly recommend just about any of the ceviches at Coast.

If you want to go all out, McCrady's is the place. The chef is kind of into the molecular gastronomy movement but he doesn't overdo it.

Have fun eating in Chucktown!

My wife and i had just had a fantastic meal @ FIG, 1 block from the market area. The meal was good enough that i will make the three hour round trip from Columbia SC to eat dinner next time i am there on business. McCrady's was good as well, the bar area has some nice banquettes.

What timing -- we're going for a week at the end of June. I'd like to hear about the dives -- bbq and seafood -- as well if anyone cares to pitch in.

Il Cortile Del Re is AMAZING! So cute and romantic. They recently opened up a sister restaurant called Pane e Vino which is also fabulous and not too expensive. Pane also has a really cute outdoor space. I'd also suggest McCrady's (the chef is up for a James Beard award for best new chef), which is a molecular gastronomy restaurant.
Hands down my favorite restaurant in Charleston is Lana Restaurant. It's actually across the street from Hominy Grill and is not open on Sunday's. It's Mediterranean and consistently excellent. Really good espresso Martini's. Plus it's out of the way from the main part of downtown and is relatively unknown.
High Cotton has really good shrimp and grits, but I'd suggest only going there for brunch b/c it is really stuffy. And if you feel like waiting, Jestine's is actually worthwhile, but I agree that there is better out there. Oh and while I'm at it, Fleet Landing is right on the water and has excellent shrimp and grits. It is a little touristy, but you'll see dolphins over lunch and that alone is worth it.
And as for SNOB, I think there is much much much better out there. For basically the same (expensive) price you can hit up Peninsula Grill and get amazing service and even better food.
A really good place for a healthy lunch is called 5 Loaves Cafe. It's cheap, small, and it's definitely all locals.
Please avoid Hymans, it's truly a waste of time and money. I'd also say skip Rue De Jean, it's overrated.
Good luck and enjoy!
***An NYC foodie who spent 5 years in Charleston***

I recommend Hominy Grill for lunch (more casual) and dinner (less casual, but that just means that they throw cloths over the dinner tables) and High Cotton for the jazz brunch. Even if you do not eat at McCrady's, the adjacent wine bar is a lovely place to have a post-dinner beverage.

In the hangover vein, we really enjoyed the Wild Wing Cafe. Yes, it has multiple locations, but fried is what you need the "morning after" . . .

Finally, if you are there on a weekend, don't miss the farmer's market on Marion Square. Lots of great local vendors, including a guy who sells stone ground grits and a nice lady who sells very tasty artichoke relish and tomato chutney.

We've been eating around Charleston for years. We never miss 82 Queen (82 Queen St.) for the stupendous she-crab soup. Go at lunch and you can enjoy the beautiful setting while paying lunch prices and not having to dress up! Their daily specials are imaginative and delicious. www.82queen.com
For South Carolina style BBQ we recommend Melvin's. There are two locations but the one we go to is on Folly Road on James Island. It's easy to reach from Charleston, just take the new bridge to Folly Beach (538 Folly Road, James Island).
Melvin's offers all sorts of side dishes with the BBQ pork ,chicken, pork ribs or turkey.
Chef Emeril Legasse and People Magazine named Melvin's cheeseburger best cheeseburger in the U.S.For non-BBQ fans the restaurant also serves chicken, hot dogs and sandwiches.www.melvinsbbq.com

I 2ed FIG, we had an excellent dinner there. We also had a really great lunch at a very small place ( a converted house) on a side street in downtown, but I can not remember the name! I think is began with a C. Long wait for lunch but it was worth the wait.