Bit of elaboration: Near the end of the series, the archives of The Word are destroyed by a (government-arranged) superstorm, and Spider's sources are all dead, leaving him with no evidence of the Smiler's corruption. Until Royce reveals he kept a private back-up of almost all of Spider's evidence, and tears through the City to rebuild what he didn't manage to save. When he gives this to Spider, not only is Spider speechless, Royce laughs in his face.
Royce: First, I want to walk into a bar and drink it. And then Iím going to start a fight with five men — and win. And then I am going to make use of a truly staggering number of prostitutes - some of whom I may have once been married to. Following which, I will buy drugs. I will, in fact, show them a large pillowcase and instruct them to fill it with drugs... And Iím putting it all on the goddamn expense account.
Spider Jerusalem's biggest probably comes near the end, when he has his showdown with the psychotic President of the United States. The Secret Service abandons Callahan when they hear he plans to plant a gun on Spider and have the agents shoot him. Spider manages to use his illness to get Callahan to confess all his crimes, and then notes that "The Smiler" has gotten sloppy.
Spider: The very first trick I ever pulled on you, Callahan. Remember? I'm soaked in Source Gas. Which is feeding directly to the news crews outside.
Detective Newton arresting The Smiler.
"Do you know what this is? It's a bowel disruptor. And you're just full of shit."
"Do not offend The Chair Leg of Truth. It is both wise and terrible."
The entire Media of The City gets one during the final arc when they decide to grow a spine and broadcast footage from Washington during Martial Law. This moment is particularly awesome:
Newsreader: Citywide, News on The Hour. First, we have something to show you. Bring the camera around Bob...
[Camera pans around to a pair of troops occupying the studio. They clearly don't want to be filmed]
Newsreader: These people are here to stop us telling you useful things. All news services in The City are currently occupied by troops from the martial law detachment. And now footage of them killing unarmed students.
Spider Jerusalem learning he has about a year until his brain completely degenerates. He takes a minute to feel overwhelmed by the news, then pulls himself together and, with his characteristic grin, promises to get the job done in that time.
Oscar Rossini, Yelena's dad, staying behind to cover Spider and co.'s escape from his mansion when the soldiers arrive. More specifically, his little speech when he steps out the front door to be arrested (all said while staring down the barrel of a big damn gun).
Hello. I am Oscar Rossini, noted city philanthropist, a supporter of the party in government, active on a dozen political committees and a substantial donor of financial gifts. I have no criminal record, several awards, three of which were given to me by presidents, and a medal. I am also, finally, a television star. I'd like it if you could arrest me now. Because it will ensure that in a week's time you will be in a most unpleasant prison with the mutant erection of a career dog rapist deep in your colon.
Fred's Heroic Sacrifice. He may be an Attention Whore but even after being made aware that he wouldn't become famous for it, he still took Spider's side in the end.