Did Wendell Wilkie split with FDR over the New Deal? I think so; I know he was an internationalist. So, depending on when his split and nomination byt he Republicans came, you could have him.
Since FDR's health wasn't always the best, perhaps he suffers a small heart attack (a la Ike in '55) in 1939. While he recovers,t he stress of the war is such he knows he needs someone else to run in his stead. Enter Wilkie, who is promised FDR's support. Wilkie therefore runs against either one of the two possible Republican frontrunners before Wilkie got the nod instead.
Problem is Wilkie died late in '44 OTL, but you could argue that being President he gets a routine checkup that catches something and this lets him live a few months longer, enough to serve out a tgerm but lets someone else win the '44 election.