The greatest upset of all time is, was and always will be the 1968 Jets beating the Baltimore Colts.
The Colts were favored by a zillion points for a reason -- the AFL had little or no credibility outside of cities where it had teams. And it would not gain that credibility until it proved it could play with the more established league.
It proved it in 1969 when the Jets stunned Baltimore. I still remember my disbelief as Earl Morrall ignored a wide-open, arm-waving, foot-stompin' Jimmy Orr in the end zone to dump a pass off to Jerry Hill. The Colts looked like the upstarts that afternoon and deserved to lose.
Pro football was never the same after Super Bowl III, with the game qualifying as the measuring stick for every NFL upset that was to follow.