Island. I must have played hundreds of games with it, but I don't think I've ever bought it as an opener (and as a non-opener, rarely) and been truly confident that it was the right play. I know the pros and cons but I have no real way to weigh them. I just rely on a vague estimate of its general power level compared to other $4s, and I tweak this very little depending on the board because I don't know where to start, even though good play would be very board-dependent. About the only thing I know is that it's a lousy way to hit $5, if that's key.
This is generally the correct way to play Island. It's a horrible opener, and still bad through most of the game except in unusual circumstances.
Vineyard was an absolute killer for me until recently. I just ignored it too much. Herald still gets me from time to time--even against lower-ranked players. Most of the other cards I can think of mostly cause me trouble against the guys ranked higher than me.
On the opposite hand, cards I see misused (or skipped) a lot:
Merchant Guild gets underbought a lot.
Mystic gets overbought a lot.
People in general aren't aggressive enough with TfB. Graverobber should be turning $5s into Provinces and almost nothing else. Forge and Salvager should be aggressively used to turn useful cards into Provinces as well.
Players don't use Mandarin very well as a late-game buy.
Island and Bishop are terrible early-game cards, but I still see them bought a lot in the first few shuffles.
And finally, Duke. A lot of people are really bad at playing it or try to just ignore it. DuchyDuke is tremendously strong on a lot of boards, and can often be bought much earlier than players actually do.