* DemonicSpiders
** The snakes can only be shot from a crouching position, and have a spit attack that they'll use when you come into range.
** The cyborgs run fairly quickly and wield rifles, which are accurate and long-range. Unless you're prepared or well-armed, it's difficult to get past them without taking damage.
* ThatOneBoss: The Enforcer, the FinalBoss of the second game, and is arguably harder than the trilogy's BigBad.
* ThatOneLevel: Several of the levels qualify.
** "Ant Town," the fourth level of Episode 2, is difficult to navigate, and has several obstaclse that are difficult to get past without taking damage.
** Episode 3 quickly proves how difficult it's going to be with its first level, "Barricade," which forces you to navigate a minefield and avoid laser turrets.
** "Mutants Attack," the seventh level of Episode 3, is a fairly long one with many snakes and other mutants, as well as [[DroughtLevelOfDoom very few health powerups]].
** "Central Command," the tenth level of Episode 3 is essentially a series of hallways connected to one central hub with a ladder, and you have to choose the right ones in order to find the shards to free the hostages. Once you do that and open the door, you have to make two fairly difficult jumps to reach the exit.