MechCommander/YMMV

Complete Monster: Colonel Renard orders his men to destroy a Gulag full of political prisoners rather than let you rescue them in one mission.
Demonic Spiders: The retracting "Long Tom" artillery guns in the first game's expansion, and any of the super-heavy tanks like the Shrek, Storm or Alacorn in the second game. The former example hides underground when you come close, but shell your mechs with devastating artillery fire in the meantime. The latter trio, on the other hand, pack heavy-duty anti-mech weaponry that can seriously ruin your day. Also, anything with Swarm LRMs, which are ridiculously accurate and shred a 'Mech's legs with ease.
Game Breaker: The salvage mechanics in the second game can net you ridiculous amounts of C-bills quickly. After battles, you are given first pick at any salvageable 'Mechs on the battlefield, but must pay a fee. This fee is only 70% of the sell price. And if you salvage it during a mission, you don't have to pay anything other than the RP cost.
- Large X-Pulse Lasers in the Mechcommander 1: Desperate Measures Expansion Pack. Relatively light, relatively common, long-ranged, incredibly fast recycling speed (rate of fire) and monstrous DPS. Equip a team of Heavy/Assault mechs (Atlas/Masakari/Nova Cat/Turkina especially), each with at least three of these babies, and watch as enemy mechs get torn to shreds under a near-constant torrent of red death.
Goddamned Bats: Hovercraft. They're generally so lightly armed and armoured as to be harmless except in very large numbers. But they can be annoying to hit and will make you waste time and potentially ammo trying to kill them.
Moral Event Horizon: Colonel Renard ordering his troops to destroy the Gulag, where innocent people are imprisoned. This disgusts even the normally calm and collected Lieutenant Diaz.