If you use multiple atlases - you're likely to encounter slowdowns on older devices, draw calls will be way higher. I personally wouldn't use multi atlas spanning with tile maps, simply to keep things deterministic.
You can't use more than one sprite collection per tile map - its been in our todo, but not super high priority as it will be a substantial amount of work to implement that while keeping things as efficient as they are now. Its more or less the same problem as above. The simplest solution is to use multiple tile maps in the same scene.
The reason multiple materials are supported right now is for solid material optimizations only, every other use of this will make things quite a bit more inefficient.
If you mostly replace tiles with prefabs, again the same thing applies. Check your draw calls.