What was the largest flop in board game history?
I'm going to use a bit of lateral thinking to answer this question - since our site is Board Games: Stack Exchange but we spend about half our time here talking about card games, hopefully a trading card game is a valid answer.

The biggest ever "board/card game flop" that I can think of is Netrunner.  Given that Magic the Gathering had recently been such a surprise smash hit, getting Richard Garfield back into the studio to produce a sequel based on ultra-cool-at-the-time Cyberpunk trappings must have seemed like a guaranteed moneymaker.  If I remember correctly, the consensus among the gaming cognoscenti was that it was a better game mechanically and production-values-wise than Magic.

And yet Netrunner sold terribly, and was cancelled a couple of years later, before its second expansion could even be released; in 1999 Pyramid magazine named Netrunner as one of "The Millennium's Most Underrated Games".  Of course there's been a happy ending to the story since then, with it having been rereleased in the form on Android: Netrunner to critical acclaim and I hope moderate success, but as gaming flop stories go, I think you'll have a hard time finding a game with bigger expectations behind it than Netrunner doing quite as badly as Netrunner did.