I haven't stayed at either but I am a big Hampton fan. Good coffee, good service, and excellent beds. Maybe stay at Hampton and eat at Clark's?
Clark's is older, but is very popular. I too like Hampton's, altho I have not stayed in any hotels in Santee. My husband is from that area, so we are there often, but stay with family. Are you spending a single night? or will you be there for a few days?
I would stay at Clark's. You can stay at a Hampton anytime. There's good BBQ in Santee too. Get off I 95 at Exit 98 at Santee, SC and go W on Highway 6 to the 1st street on your left which is Britain. Turn left and go to Maurice's for good BBQ. Get off I 95 at Exit 98 and go W on Highway 6. Take a right on State Park Road and go to Lonestar BBQ for good southern food. Clark's Inn and Restaurant is also a fine place to spend the night and have breakfast, lunch or dinner.
Maurice's Gourmet BBQ @ 263 Britain St, Santee, SC 803 - 854 - 3889.
Lonestar BBQ @ 2212 State Park Rd., Santee, SC. 803 - 854 - 2000
Clark's Inn and Restaurant @ 114 Bradford Boulevard, Santee, SC 803 - 854 - 2101.