Richard Russell in 1948. Bobby Kennedy in 1968, Ted Kennedy against Jimmy Carter in 1980. Russell began the long process of the Dems' de-Dixiefication, RFK toppled LBJ, then EMK helped dent Carter even further. GOP hasn't had a successful (in terms of dooming an incumbent) challenge since 1912. If a President is weak enough that such a challenge becomes viable, it doesn't bode well in the general election.