Chapel + Witch

I got absolutely destroyed the first time someone pulled this combo on me.  The idea is to get the chapel card to thin out your deck by trashing all your estates and coppers keep enough to pick up silvers.  When you finally have 5 coins in your hand, you pick up the Witch.  Because your deck is so thin, the witch essentially appears almost every turn or two turns and you can curse your opponents to death.  It is so fast and annoying that it totally kills your opponent's strategy.  

From my experience, most players then attempt to get retaliate by getting witches themselves.  But by this time, you already have a head start on the curses and you focused them to change their initial strategy which is exactly what you want by playing this combo!