Are they looking for peace & quiet, or partying/restaurants? Are they more into hiking and activity or just kicking back? Foodies or bbq-junkies?
Have they spent time in Nashville? That might be a fun jump-start or finale. Nashville is a blast if you like live music at all.
Drive times on WNC can be slow, but worth it if you like the views, hiking, etc.
One option is to enter near Joyce kilmer memorial park and 'tail of the dragon' on your way to nantahala outdoor center (rent duckies for their class 2/3 rapids). Then wind around to cashiers, highlands, sapphire toward brevard hitting up all those waterfalls and hikes in that area (and transylvania county).
From there i'd go up to Asheville and do it's highlights and blue ridge parkway, then head to the beach, stopping in Ch hill for the bball museum.
Could do blowing rock and that part of blue ridge parkway (linville, grandfather mtn, julian price) on the way back. I've never been to great smoky mtns nat park, but you might as well route thru there on the way back west.