I would guess one of the first was the second BOAC 747 route, which was from JFK to Bermuda. The same aircraft would manage LHR-JFK-BDA and return within 24 hours, so it was operated from day 1. Nobody goes to Bermuda except on holiday, do they ?
AS BOAC crew I used to work my nuts off on the JFK - BDA -JFK 'Bermuda shuttle' route. It was hell, full of Americans going on holiday and we had to do a full meal service and duty free in such a short time, but as crew we did it and had a deservesd day off in the Lexington before going home the following night.