One of the things I find frustrating is that there's no reliable way to defend against contact-damage-immune threats that invade internal spaces, like worms and centipedes, and their eggs- needlers can't target them, and tentacles can only attack their own square, so you can only watch as they chew through critical body segments, and spawn more from also untouchable eggs.
Something like an organ or evolution that negated contact damage immunity for nearby tiles, or that allowed tentacles to protect neighboring tiles would be game-changing.