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The Harvesters. Giant robots that may as well be Eldritch Abominations due to their function and unstoppability, plus that their primary ships in the fleet consists of smaller cube-like robots that combine to form larger ships and weapons, as well as the fact that they upgrade themselves, making them even deadlier.
Made even worse that they're sent by the humans remaining on Earth to go out to colonized worlds and "harvest" the inhabitants, i.e., killing them and ripping them apart for the organs so the people on Earth could use them.
The Final Harvester ship, which according to Rabat, its purpose is to destroy planets no longer needed by the harvest fleet. It also contains the Paksis that was left on Earth, which spoke through the body of a young boy, which after Hibiki mocked the Paksis for its stubborn views, it went insane and attempted to destroy the entire galaxy with an out of control wormhole, with the end result that Super Vandread barely makes it out alive thanks to Nirvana's own Paksis Pragma protecting it with a net-like shield.
Meia's claustrophobia. It's particularly jarring given how lighthearted the series was up to that point.