A - Too simple, too high contrast details. If you want to do flat shapes I would go full-resolution and definitely do the whole game with flat shapes.
B - Looks more like a sci-fi computer core than a building, but I think that's mostly because of the stripes.
C - Kinda cool. Details seem a bit of a hodge-podge. I'm not a fan of mixing totally different perspectives—in this case straight top-down for the building and an oblique projection for the windows and details. Especially with those left side windows it looks pretty weird.
D - A bit plain, but it works. Definitely the clearest.
E - Also decent and a nicer design, but the dark edges make it very hard to see.
I guess my favorite perspective is the flat one in E. D and B aren't too bad, but C looks pretty wonky to me. I think you can use the cast shadows to get a decent sense of depth with a flat top-down perspective.
Some general points:
- I would use black for the building outlines and either not use outlines for the inside details, or do them with a different, lower contrast color.
- You need more color variation and texture. Right now they're all very plain and flat, which makes them look boring and artificial. Add some things that aren't just gray. Doodle around with random colors at low opacity. Think about where dirt, grime, and rust might accumulate. Also consider repairs, random debris, etc. Even if you want a clean setting, some subtle variations can make things much more interesting.
- Think about your light direction and shadows more. You have slanting roofs, but they aren't shaded to match the light direction that is shown by your cast shadow. Also the lighting and shadows on the details don't match the shadow of the building.
- If it's night I assume the shadows are from moonlight. You could make the light blue for some nice cool-light/warm-shadow contrast. (not exactly realistic, but people don't know that.)
- I like the cast shadow of D the best, though I would make it a little bit soft at the far edges (and not weirdly rounded at the building corners of course).
- Will this game have lighting effects that allow the player to see better? If not, I wouldn't go darker than the top image, the bottom one is much too dark to see anything.
I doodled over this a bit, mostly just on D. Here's the before and after: