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- The NPC D'deridex-class battleship has a nasty move where it captures the player's ship in a tractor beam, then fires three plasma torpedoes in quick succession that will destroy even the toughest ship while it sits helpless. If you can't stay out of range (5 kilometers), your only hope is to shoot down the torpedoes before they reach you, or use Hull Polarization to break free and run for your life. They also have the Viral Matrix ability, which launches a probe that disables your ship's systems (such as weapons or engines) for a few seconds. Along with a Tractor Beam (if you get close enough) and a few Heavy Plasma Torpedoes, they can be very annoying.
- The Borg. At maximum admiral level with the top tier weapons, shields and extras, and all the right skills, you can take out a single Borg cube. But it will drain the hell out of your shields and hold you in a tractor beam while doing it, all while burning through your hull and lobbing extremely devastating torpedoes at you. Expect to be at half hull strength by the time the battle is over. Plus you'd better be far away when it dies or the blast will finish you off. If you end up facing anything more than a single Cube (even a cube and a few probes, or a cube and a sphere), you will barely survive if you choose to run instead of fight. And if you blunder into a Borg fleet of two cubes or more, you'll become a rapidly expanding vapour in less time than it takes to order "Evasive! Emergency power to engines! RUN FOR IT!".
At least, that's how it used to be. The NPCs haven't kept up with the Power Creep and now it's not unheard-of to have players soloing entire groups in Borg Invasion dailies. And then Cryptic fell back on using the Borg for The Worf Effect when the Vaadwaur were introduced, just like Berman and Braga had done when Species 8472 was introduced.
- The True Way have the Keldon Class. While on the lower end of the Demonic Spiders scale, they have a number of very cheap moves that can make them hard to beat. For example, they can crap out three "photonic Galors," hit you with a massive torpedo spam attack that will make you wish you could hit the "brace for impact" button faster, and attacks that will drain your shields rather rapidly.
- Most likely set up intentionally with Voth starships, at least if you're flying a typical Glass Cannon-build tacscort. They build Mighty Glaciers that can put up an indestructible shield that will outlast most escort Alpha Strikes (and with higher-level mobs, actually pays the damage back), and their Beam Overloads and transphasic chroniton torpedoes hurt. The frigates also have an ability that strips the shields of enemies and messes with their sensors and maneuvering the first time they're hit after spawning. More durable cruisers that can tank the Voth firepower, and more careful players who are ready for their particular gimmicks (the shield-stripping lightning thingy can be cleared instantly with Science Team), have an easier time.
- The updated Undine starships are also this. Their Beam Overload attacks will knock you back hard if you're struck by one, their High Yield Torpedoes will grind your ship to a halt and that's not even counting the fact that they're one of the groups who will pull off the nerve wracking Chain Holds on you (this time by means of pulling fluid from fluidic space into realspace, slowing ships and eating their hulls through shields). Undine cruisers can also Teleport Spam.
- Tzenkethi ships have special shields that are significantly stronger aft than forward, enough to soft-counter the flanking bonuses that "raider" ships (mainly birds-of-prey) and Intelligence-specialized captains get from Chasing Your Tail. This means you're mostly forced to attack them head-on, which naturally is where their biggest guns are. Now factor in that smaller Tzenkethi ships are set up to buff and heal nearby heavy hitters, and you've got an enemy tailor-made to counter many players' favorite tactics (Gravity Well + Area of Effect attacks).
- Klingon Swordmasters almost always make a beeline straight for the player, outright disregarding the rest of the landing party, no matter how well they've been armed. This wouldn't be a problem, except for the fact that Swordmasters are dual disruptor pistol wielding, BFS-carrying, seriously pissed off damage sponges capable of killing players in seconds at lower levels. Such as all of the Lieutenant grades. Note that every enemy you encounter has their own badass Mook equivalent, but for the majority of the early game, the Swordmaster will be the bane of many a PCs existence.
- Fast forward to the next step in the Sorting Algorithm of Evil and you'll meet the Reman captains, who can spawn telepathic clones of themselves and attack with shield-piercing psionic attacks. Even at low difficulty levels, many players have complained of wiping again and again against these guys.
- The Tholians. Go to down to Nukara in the Neutral Zone. You'll see why after being chased across the map by Tholians you happened to be within 100 feet of 5 minutes earlier.