Yeah, on the rare occasions I play 3p & 4p games anymore, I do lose to novices from time to time. All my heuristics are optimized for 2p, so my instincts sometimes fail me in multiplayer.
Though I had an amazing recent game with 2 novices, one other very good player, and myself:
We all opened Pirate Ship, both novices got lucky, and the other two of us got super unlucky. My Ship got discarded 6 shuffles in a row, leaving me with $1 on my mat by the time almost all of the coppers were gone. The novices were at $4 and $5, and the other good player was stuck at $2.
In the meantime I focused on Native Villages, eventually saving 3 of my Coppers on my mat and emptying my draw pile so that I
finally saw my Ship in hand for literally the 2nd time in the game. The novices had started thinking about Colonies, buying up treasure again. I played my Ship and was lucky enough to hit a treasure and get up to $2. Next turn, I picked up my Coppers off the mat, played my Ship for $2, and bought a
Mountebank. Nobody else had bothered to buy one! hehe...
Native Villages and Pirate Ships were empty, but the other good player was in no position to end the game, and the novices were too focused on Provinces. Eventually I got several Throne Rooms (playing TR/Mountebank most turns) and 8 fully powered Cities, having absolutely destroyed everyone's deck with Mountebank. I ended up with most of the Colony pile for a resounding victory. Game-end condition? I finally succeeded in emptying the entire Curse pile with Mountebank.
It may have been enabled only by very poor play, but it's probably my favorite ever come-from-behind win