Inspired by a recent conversation:

Never before and never since have the stakes been higher than when the Borg set about invading Earth. The Borg returned as villains and even menaced Earth again, but the scope was never as grand nor was the threat ever as palpable as in this two-part episode, a point which was underscored by the destabilizing of the familiar crew.

The first half of this two-part episode is decent but serves primarily to set up the phenomenal second installment which sees Patrick Stewart deliver what may be the all-time greatest performance ever shot for TV as he is physically and psychologically tortured by his sadistic Cardassian captor.

Another Patrick Stewart showcase, this one finds him living an entire lifetime as a farmer in the span of the one hour episode, while Captain Picard lays unconscious on the bridge floor. Sadly, the promise of deep characterization opened by this episode was never really seized by later writers who seemed either unwilling or unable to explore the ramifications of Picard's experience -- his past experiences as Picard were always treated as more real than his experiences in his alternate life.

The definitive Data episode came early in the show's run, when Roddenberry's touch could still be felt; this episode dealt with the difficult question of defining 'life.' Later portrayals of Data could never think up anything better than the themes raised in this highly philosophical episode and just mimed its themes incessantly until Data wasn't a character as much as a caricature. Still, you can't beat the punch of the original episode even though its theme has been diluted over the years.

This two-part season-straddling episode about the turbulence in the Klingon's high council and Worf's quest to restore the honor to his family name always seemed really cool to me. The Klingon civilization is so much more developed than any other nonhuman Star Trek civilization, it's fascinating the see the political and social machinations of this imaginary machine.

Honorable mentions:
Tapestry, Family, Yesterday's Enterprise, All Good Things, and Shades of Grey. (Just kidding.)