The big bad in our last campaign was a female lich. After taking some liberties with the official time/storyline to make it my own, she ended up doing what almost nobody esle in Faerun could do...she nearly destroyed Waterdeep. I played out her machinations over 12 or so levels and put the PCs through such emotional hell that they were completely different people than when they started.
Unfortunately, luck was on the players' side in the final battle and a single undead-slaying arrow spelled the end of this, my most favored and cherished villain. Good thing, too....they faced her about 7 levels earlier than they "should" have (I decided "well, if they're gonna bum rush her, let 'em get what they deserve") and the rest, as they say, is history.