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Goddamned Bats: Swarmers. These appear in large groups, and while weak, they're fast and require that you either use a Splash Damage/Chain Lightning tower (the latter of which chains less than half the time), or build lots of weaker towers and therefore making your strategy weaker to armored units (while spending money on towers). Furthermore, these easily distract your towers from attacking the stronger enemies. Thankfully, Swarmers do not do much damage to your Mana.
Game Breaker: There a concept known as supergems, which are specially constructed gems to maximize damage output for as cheap as possible. Such a construction is practically the only way to hold back enemies for all waves in endurance missions (Gemcraft 0 or Labyrinth). The exact construction differs among the different Gemcraft versions, but the most common method is combining a gem with another gem that's two grades lower.
In Labyrinth, there are two common tactics. First is using the Red Bloodbound gem, which increases damage based on a percent of total kills. Next is the Lime/Yellow combination, which hits multiple targets with a damage multiplier.
The red gem in Labyrinth isn't a let down by itself, because it gains increased damage based on the percent of total kills, allowing it to deal extreme amounts of damage with enough kills.