In terms of the popular vote, it would be the Election of 1964

LBJ got 61.1 percent of the vote. Goldwater got only 38.5 percent of the vote.

In terms of the electoral vote, it would either be the Election of 1936 or the Election of 1984

In 1936, FDR got 523 and Alf Landon got 8

In 1984 Ronald Reagan got 525 votes and Walter Mondale got 13

EDIT: Actually it looks like 1936 was also very lopsided in terms of the popular vote. Even more than 1964

FDR: 60.8 percent Landon: 36.5 percent.

EDIT 2: Ok sorry again but it looks like the election with the biggest popular vote percentage margin between the 2 major candidates would be the Election of 1920. This will be my last edit on this I promise!

Warren Harding (Republican): 60.3 percent James Cox (Democrat) : 34.2 percent