Eight Men Out by Eliot Asinof (1963) — The definitive account of the 1919 Black Sox scandal that ended the career of Greenville's most famous son, "Shoeless" Joe Jackson. Asinof interviewed participants and reconstructed the conspiracy in detail. Read it before visiting the Shoeless Joe Jackson Museum in the West End and the picture changes considerably.
The Prince of Tides by Pat Conroy (1986) — Set in the South Carolina Lowcountry rather than upstate, but Conroy's immersive writing captures the weight of Southern family history and landscape better than almost anyone. His work is the essential entry point for understanding the culture of the state.
Edisto by Padgett Powell (1984) — A Southern coming-of-age novel set on the South Carolina coast, spare and sharp, with an ear for the rhythms of the state that makes it worth reading before or after any time spent in South Carolina.