Re:Atlanta to Charleston, SC and back.
jfk if you're looking for a quick stop off the interstate and you like Mexican, I eat at Taqueria Jalisco (612 St. Andrews Rd, Columbia) at least once a week, for like the last five years now. Get guacamole, sopa de pollo, and something with shrimp in it (I like the quesadilla). They have agua de jamaica and horchata and a great dessert called bionicos. I just love them. Their salsa has been a teensy bit off lately, but this is an amazingly consistent place.
Any Rush's Hamburgers will make you very happy--get a chili cheeseburger and a shake. Zesto's in Triangle City (West Columbia) is the best place for fried chicken, and they just expanded their dining room and parking lot once again. Rush's is fine at any location, but Zesto's really is not.
If you are looking for something schmancy, I would recommend either Hunter Gatherer near the USC campus or a brand new place I just tried, the 116 Espresso and Wine Bar on State St in West Columbia. We went with some work colleagues a few weeks back and found ourselves wiping plates with our fingers to get every last little bit. We had what was advertised as a cioppino but in a creamy sauce, but it didn't matter because it was gone in a few minutes anyway. They have a warm blue cheese dip that was crazy good, and there was a pizza that I didn't get that I now miss. The desserts were out of this world, and several of my companions got their specialty bloody Marys and were making serious noises over those.