Do you want on the beach? or intercoastal by marinas? Is just middle of island okay? Do you want to be near newer sections or in a plantation or near the old classic area? Do you plan to do anything there other than sleep / eat?
EDITED TO ADD: Based on suggestion below of Montage - What is your budget? And do you mean on Hilton Head Island or in areas surrounding the coast there?
Also look at maps, it's not right off the interstate, you'll add a substantial drive to that, close to an hour, sometimes longer if during busy times.