Some advice from my own experience: Z-order every 2 or 3 ticks and only object that are on screen or within a distance. You wont notice it. You will have to Zorder all first, then set to front limbs and other parts that are suppose to be in front of parent objects. As for the amount of enemies on screen, just don't have to many of them on it, and try not to process them outside of the screen. But keep in mind that you can't do any transformations of pinned objects, so what i do, every second or less, i pin other parts of characters that are off screen, and when they come back on screen i unpin those and other events set them to their place. Loads of messing about really. I wish construct would have some tools to create entities from several objects. Anyway, it's doable. As for pathfinding, you have an option to create game on a grid, and use A*, but even the behavior shouldn't put too much pressure on the performance. You could switch between pathfinding and other movement behavior depending on circumstance.
But here's what most annoying will be for ya, and that's collisions with solid environment. This is a nightmare right now for isometric games. Using any of available plugins will give you poor results: it will bounce your character or it will move it at nearest angle but at different speeds. So i created my own collision system, a long one, that checks offset. I only did that for player, but will have to figure out how to make it general now. This is the only way I could get normal resoults, making player
I have also one for the pad, but that one is different. It was even harder to come up with
And btw, someone generous could turn this in to a plugin, so we finally have something NORMAL for collisions.
Also, if you want some distopian soundscapes, I'd can write some gritty, grainy tracks.