I think it was reading Future Quest, based on Greg Hatcher’s recommendation, that got me thinking of how many spy cartels were operating in 1960s fiction. Blame of course, goes to the Bond films giving us S.P.E.C.T.R.E., then The Man From U.N.C.L.E. spreading the Bond tropes further, pitting agents for The United Network Command for Law Enforcement against T.H.R.U.S.H., an acronym a friend of mine says wasn’t defined until the comics (Technological Hierarchy for the Removal of Undesirables and the Subjugation of Humanity).
Future Quest put me in mind of it because the Hanna-Barbera hero roster includes Birdman, so naturally we have Dr. Zin from Jonny Quest working with Birdman’s acronymic adversary F.E.A.R. — never defined, but you can see it on the shirt of F.E.A.R.’s Number One.
Apparently F.E.A.R. had an English branch as British spy-hero the Steel Claw, who becomes invisible when his artificial steel hand conducts electricity into him battled the Federation for Extortion, Assassination and Rebellion multiple times (art by Jesus Belasco).
Similarly, Superman battled D.E.M.O.N. — Destruction, Extortion, Murder and the Overthrow of Nations —
—and so did the Mighty Crusaders at MLJ (covers by Curt Swan above, Paul Reinman below) —
— though the Nameless One’s D.E.M.O.N. stands for Destruction, Extortion, Murder, Oppression, Nefariousness. Sounds like they changed the meaning just enough to avoid an evil-organization trademark infringement suit.
Jack Kirby, of course, gave us Hydra and S.H.I.E.L.D. with their amazing arsenals—
—then Marvel followed up with “Them” and the Secret Empire (cover by Kirby again) —
— which later turn out to be the same organization.
Over in paperbacks the Shadow battled CYPHER, a crime cartel of former military officers pissed off about things like their countries giving up empire. 
Lois Lane took on S.K.U.L., the Superman Killers Underground League as Commander Benson details and Kurt Schaffenburger depicts.
As Derek Flint, James Coburn worked for Z.O.W.I.E. (Zonal Organization World Intelligence Espionage) against Galaxy, which surprisingly was not an acronym.
Also surprisingly, Fred Flinstone’s adversaries in The Man Called Flintstone didn’t get a cool name, although their evil leader was known as the Green Goose.
The Inferior Five came to the aid of C.O.U.S.I.N. F.R.E.D., an UNCLE parody (I missed the joke as a kid that Mr. Waverly’s counterpart is Mr. Ivanhoe — Waverly and Ivanhoe are both Sir Walter Scott novels), against H.U.R.R.I.C.A.N.E, a parody of the T.H.U.N.D.E.R. agents. As you can see, Mike Sekowsky’s and E. Nelson Bridwell’s splash page got in on the fun. No, I’m not going to spell any of those out.
The Archie gang, never ones to miss out on a trend, became agents for P.O.P. to fight the evils of C.R.U.S.H. I don’t know what the acronyms stood for. Covers by Bob White (above) and Bill Vigoda (below)
And back in the paperbacks we have L.U.S.T., H.A.R.D., T.O.M.C.A.T., O.R.G.Y. and of course Agent 008 of S.A.D.I.S.T.O, the Security and Administration Division of the Institute for Special Tactical Operations.
I know I’ve only scratched the surface but I’ll stop there. I only have so much time, after all
#SFWApro.
I think the THRUSH acronym first appeared in one of the Man from U.NC.L.E. novels (the first one written by David McDaniel).
Otherwise, my favorite bad guy organization acronym is not from the ’60s, but rather the late ’70s in a Saturday morning cartoon called Drak Pack: OGRE, or the Organization for Generally Rotten Enterprises.
I remember the Drak Pak but not the acronym. Aquaman fought an OGRE a couple of times — Organization for General Revenge and Enslavement. Drak Pak’s wording was more amusing.
Archie’s agency was POP: Protect Our Planet, as well as the WPA (World Protection Agency) in some stories. CRUSH went undefined, just like THRUSH, on the Man From UNCLE. HYDRA was the same, in Nick Fury, Agent of SHIELD, though AIM was Advanced Idea Mechanics, from the start.
As Edo said, David McDaniel created the name for THRUSH, in the 4th Man From UNCLE tie-in novel, The Dagger Affair. It was said to be descends from Professor Moriarty’s organization, in the Sherlock Holmes stories.
The THUNDER Agents mixed spy-fy and superheroes, with THUNDER standing for The Higher United Nations Defense Enforcement Reserves. They fought the Warlord and his minions, then fought an organization, called SPYDER..
Lancelot Link worked for APE (Agency to Prevent Evil) and the villains were CHUMP (Criminal Headquarters for Underworld Master Plan).
Matt Helm worked for ICE (Intelligence and Counter Espionage) and his enemy was Big O.
Mike Grell joked around with this kind of acronym construction in a Jon Sable storyline, where Sable assembles a mercenary team to do a recon of Nicaragua, looking for evidence of Soviet weapons coming into the country, for the CIA. One of the team members says they need a name, like the A-Team (which was on tv, at the time of publication) and another suggests Worldwide Airborne Response Team and the first guy says, no that would be WART. So, the second guy counters with Fast Action Response Team and the first rejects it again, for the obvious reason.
I knew someone would fill in the gaps. I was a big fan of Lancelot Link as a tween.
Hydra was never an acronym though — the “cut off a limb and two shall take its place” shows it was a name. Using the hydra as a metaphor for subversive forces goes back to the 17th century. Whether Lee or Kirby knew that or not they were following in a proud tradition.
My all-time favorite acronym group name is the Nihilist Anarchist Horde (NAH). They were mentioned in passing in Robert Anton Wilson’s Schrödinger’s Cat Trilogy (I think it was in the first book, The Universe Next Door, but I read those books so long ago I may be misremembering).
Captain Carrot had a parody group ACROSTIC, A Corporation Recently Organized Solely To Instigate Crime.
THRUSH was initially going to be called WASP, but the producers changed their mind. That acronym remains, though, in the theatrical movie edit of the pilot episode and another.