I know, there are many cons against the below ideas, but i think some realism should be discarded for the fun.
Invincibility
This is an old problem, player with decent armor cannot be harmed. This change the monsters from a dangerous enemy to an annoying obstacle. Risks should never be gone. It would be a nice change if some percent of damage could bypass the armor anyway, until someone figure out a good solution.
Item resistance
The item damage resist calculation is easy and simple, but it has its shortcoming. High resist items almost never damaged, which makes them just a perfect items forever. Item quality value should be change to a hit point value, calculated from the matters of the item. This would make every item vulnerable on a long run. Also items should be wear out from use. Repair should more difficult - or less successful - on an item which need a high level of skill to create. I really miss the constant repairing like in the Fallout games.
Fire
Nerf fire damage. Nobody dies from it, only the zombies and they are already pathetic.
Damage
Many monsters have a difficult time to kill the character while others can easily kill them. I think monsters should be wear down the character, damage should be low and healing should be slow or difficult. It would require more planning on a long run as the problems add up, but also permit more mistakes in a short time. Don’t starve use similar solution, most creature can’t kill you outright (well, a basic armor doesn’t harm), but health wearing down on long run without healing items.
High damage
A high damaging attack should be change to a normal and a rare special attacks. Normal “High damaging attacks” should be a low damaging but armor penetrating attacks, so they will be challenging even for an armored character, but still not deadly. Special attack should be high damaging, but evadable.
Weak special attacks
I love special attacks, they make the game interesting, but they are too frequent and not punishing enough. Most of them are just a minor setback for a short time. They should be rarer but more dangerous. I would like to see a much rarer but cripplingly painful poison bite, maybe for a full day.
Early warning
There should be a warning before the special attack and there should be a way to evade that. If the player failed to evade it, it should be an automatic success for the special attack. A hulk smashing attack or a zombie bite would be defeated if the player steps away from the monster. Chicken walker grenade attack should be “slow targeting”, player should see the slowly moving laser point, so constant moving would defeat the special attack. The games come to my mind with similar features are the Doom the roguelike and the Don’t starve.
Levelling
I loved the game because it was a levelless game. But the constant “new power item” problems forced the developers to “evolve” the monsters, so they can challenge the player character. I think this is a wrong direction, because it has no ending, there would be always a new power item, which would need a new monster for the challenge. Less damage from the monster attacks, more meaningful special attacks and not full damage stopping armors would make a constant challenge.
Abundance of items
Abundance of items is very helpful at the beginning of the game, but items should be gone with time. Bring back acid rain with an early warning message or just make weak, item consuming monsters (acid blobs, item chewing monkeyman, aimlessly wandering, building destroying, item stomping, neutral golems, anything) everywhere. As time goes, new places should be less chance to spawn items as the monsters already eat them. I know it is forced and silly, but i think self sufficiency is a major part of the game, and it is currently defeated by the large amount of free items.
NPC
Change wandering npcs into some kind of strange, intelligent cthulhuish aliens until their code is finished.