The Chapel Hill/Carrboro/Durham area has a great underground/alternative music scene. (Pittsboro even has a new venue that is garnering some attention for underground bands and performers.) But I have no idea how someone wanting to break into the mainstream from the ground up would fare. A number of bands have gotten a start here one way or the other. (Back in the day, the UNC college station was instrumental in getting U2 exposure to US audiences.) James Taylor got his start here, along with the Connells, the Squirrel Nut Zippers, Superchunk. Leon Redbone lives in Pittsboro. which I didn't know until recently. Winston-Salem seems to have more of a Rock scene, but I don't know much about it. There is a huge annual festival called the Heavy Rebel Weekender in W-S, catering more to Punk, Rockabilly, and trad Country than Rock, though.
I was on the periphery of the music scene in South Florida for a number of years (writing for a local webzine), and I found that unless you are in a popular genre (Electro/dance, Pop, Hip Hop, etc.) many venues there are not band-friendly. They preferred to make more profit with DJ's or might feature a well-established band every so often, but gave short shrift to local bands. I know of a couple of bands that went nowhere in South Florida for years, and ended up getting signed elsewhere! You also have a lot of cheesy "reunion" tours from 70's/80s bands there. But I was more involved in the underground scene, not Rock-oriented genres, so it may be a bit different from your situation. Orlando seems to have more larger shows.
Some bands formed consortiums and their own labels to market their music, and were then picked up later by major labels. The Decembrists are a good example.
I wish you the best of luck!