The James Bond RPG couln't use the infamous S.P.E.C.T.R.E. for licensing reasons, so used a Suspiciously Similar Substitute; Technological Ascension, Revenge, and Organized Terrorism, or T.A.R.O.T.
Exalted has a very powerful Necromancy spell, typically only used by antagonists, that functions as a One-Winged Angel transformation immediately upon what would ordinarily be their death. Its name? Birth Of Sanity's Sorrow.
GURPS Illuminati included a sidebar on an organization that called itself "TRI", which stood for Three Random Initials.
Subverted in GURPS IOU, which stands for Illuminati University. People asking what the O stand for are told they're not cleared to know.
Not to mention an entire department called C.T.H.U.L.H.U., which stands for College of Temporal Happenstance, Ultimate Lies and Historical Undertakings.
GURPS itself is the Generic Universal RolePlaying System.
Prior to release, it was referred to as the "Great Unnamed Role Playing System" in at least one of SJG's publications.
On a side note, this editor once was the Game Master of a GURPS Space game and once had the players encounter a race of space monkeys, which had cannons mounted on their ships that fired Projectile-Organized Operational Protoplasm...
Battletech has a couple fun acronyms, one that has been expicitly explained and one that is merely fun. Myomer Acceleration Signal Circuitry is a movement booster, while the NARC Missile Beacon has never been explained.
Rifts Chaos Earth has the Northern Eagle Military Alliance
In the main setting, there's a famous suit of Powered Armor called the Strategic Armored Military Assault Suit.
Monsters And Other Childish Things has the Monster Investigation Bureau, which is tasked with capturing and studying what they call Biological Extraterrestrial Merchandise — if you don't get the second one, that more typically stands for Bug Eyed Monster.
The game S.A.V.A.G.E. = Survival And Victory After Global Extinction
GORE, or Generic Old-school Role-playing Engine
There is an Earthdawn adventure titled Terror In The Skies.
