The Griffey trade.
I drunk the Kool-Aid after the '99 season and was convinced that Junior was the magic potion this team needed to storm to the WS. I ignored all of the red flags the pitching staff had thrown up, figuring there was no reason they couldn't duplicate their success from '99. Well, the team didn't completely tank, but they didn't come within sniffing distance of the WS, and, well...you all know the story of the last 5 years.