Well I can't think of any episode where just one single antagonist came very close to succeeding on his or her very own; but in that Christmas special A Creature Christmas 3 of the bad guys basically kicked the team's butts at least at first, the villians even managed to hijack the Tortuga and all of their stuff including their CPS's.
Then left the team stranded on an ice floe in the middle of a freezing ocean with seemingly no technology; luckily Martin still had that little un-opened present in his pocket that Aviva had given to him which was the key to their way out, that being a little key chain device which can summon their gloves and vests to them no matter where they are in the world.