I guess it depends on how much time you want to spend on the interstate. I live just north of Jacksonville and my preferred way is to go up through Brunswick, then take US 341 to McRae. You then take US 441 around Athens, up through Franklin North Carolina to Cherokee. From Cherokee, take US 19 in Maggie Valley.
If you're in a hurry and want to stay on the interstate, take I-95 to I 26 in South Carolina, take I 26 to Asheville, and then a little west of Asheville on I 40 you can get to US 19 and follow it to Maggie Valley.
I prefer the less traveled roads although they are very good roads all the way up. Best time to travel is during the week although you will see more truck traffic especially on US 341. Depending on how long you want to stay in the seat there a number of options for lodging - I usually stay in Milledgeville just to break the trip up. This route also has plenty of places to stop and stretch your legs, have a bite to eat, etc.
If you're looking to explore other areas as well as get to Maggie Valley, you might look at Robbinsville as part of the trip. I am looking forward to my next trip as soon as it cools off a little and I know you will have a good time. Let me know if you need any other details.