Doesn't have to be a stand alone, but not looking for best arch, or best run, or anything. Just what single issue sticks with you.

Mine would be Watchman #4: Watchmaker. Blew me away the first time I read it, and in subsequent reads still has a huge impact.

A very close second would be Fraction's Hawkeye #11. Pizza Dog is such a good character and what Fraction did without words was incredible.

The speech writers did a great job of knowing how to put quarters in the Republicans to set them up. Biden gave the speech well, but the unsung heroes need love, too.