1. "I Am The Most Unpleasant, Rude, Ignorant And All-Round Obnoxious A***hole That Anyone Could Possibly Have The Misfortune To Meet."
Episode: The Sign Of Three
Directed At: Himself
Don't make the mistake of thinking Sherlock, arrogant and self-assured though he may be, is above self-deprecation. Undoubtedly the most on the nose and biting of all his insults, this one is squarely directed at himself. And what better time to point out one's own flaws than during a best man's speech?
For all its rudeness and profanity, this line is met with some semblance of a warm response, as it comes after a rather ill-timed denigration of the concept of marriage and is swiftly followed by a very moving and affectionate tribute to the union of John and Mary he's using his own faults to highlight John's strengths as a human being in an episode that's essentially a 90 minute tribute to the role of Dr. Watson in Sherlock's adventures. Who would have thought one of Holmes' trademark put-downs could be turned into something so lovely?