Master of Orion/YMMV


 * That One Boss: The Crystal Life Form from the first game, sort of. Triggered by a random event, it could appear anywhere and anytime. If you didn't have a big, heavily armed fleet of Large or Huge ships armed with not-missiles? Hope it doesn't approach your territory. Or appear right inside it.
 * Demonic Spiders: If you let the Psilons develop unopposed, they *will* climb the tech tree. This is usually followed, at some point, by them climbing all over you, guns a-blazing.
 * Fanon Discontinuity -- The third game. This included a LOT of backstory that had never been hinted at in the previous games and never mattered in this entry either.
 * Game Breaker:
 * Plenty of them, but outstanding is the Phasing Cloak-Time Warp Facilitator combination, abuse of which leads to ships that can wipe out the Antaran Fleet, solo, several times over. Of course, by the time you get all this technology, you've already pretty much won the game anyhow.
 * There's also the "Orion Globe" design in MoO2, a Death Star-sized battleship that forgoes the typical Stellar Converter for a combination of scanning equipment and refined weaponry that allows it to sheer through all forms of shields, armour and defences, wiping out whole fleets in a number of turns.
 * The Psilons in MoO 2, if AI controlled. They have huge bonuses to scientific research speed, and gain automatic access to every technology in the game rather than having to pick and choose useful techs from a catalogue of options based on the situations they encounter. As a result, by the middle of a long game an unmolested Psilon empire can expect to be unambiguously more powerful than any rival empire, and by late in that same game, the Psilons can expect to have grown so overwhelmingly powerful that they can effortlessly defeat even alliances of all their rivals.
 * Custom races could pick relatively minor flaws that technology would eventually render harmless to pick up loads of superpowered skills, but the greatest gamebreaking trait for them was Creative. This gave you the Psilon advantage of picking up every possible application from a scientific advancement. Even without the fast research bonuses the Psilons have, Creative is absurdly powerful. And custom races had nothing to prevent them from picking up those research bonuses; a lot of optimized race builds for MoO2 were basically "Psilon 2.0".
 * Goddamned Bats -- The Darloks. If there are Darloks on the map, you will get constantly framed for espionage against other factions.
 * Nightmare Fuel:
 * The Antarans. Seriously, you'll be watching over your empire, minding your own business. Next thing you know, the music changes to an ominous tune, and Space-Cthulhu is in your face, giving you a heads up before ravaging a colony.
 * The space amoeba. Sure, it looks stupid and most of the time its just harmlessly floating around impeding your attempts to colonize other planets. But then they actually attack. Big whup, what permanent damage
 * Ruined FOREVER -- MoO 3 elicited this reaction from a number of hardcore fans during development. Then it was released and promptly bombed, suggesting that it really did suck.