We can't really tell how integration works with every third party package that exists on the asset store.
The Mecanim integration (SkeletonAnimator) is already full of hacks as it is since Unity doesn't expose quite enough in their API just yet and Spine Animations aren't Unity-serialized. Better integration will probably happen when their super-flexible Playable API is released with their timeline feature.
Right now, multiple skeletons is best for Spine workflow but it won't work cleanly with Mecanim and likely with third-party stuff, without needing to add the right code. Particularly, you need to manage the swiching between the different skeletons and manange finding which skeleton plays which animation you want.
So the recommendation is really to write that code, so Spine and your third-party thing can talk to each other the way you want and the way they need to.
If you stuff all your directions and animations in one skeleton, it will be a nightmare to work with and it will take the artist/animator forever to get anything done.
This is true unless your chosen style is very, very, very simplistic. (ie, very few bones and images.) In which case, you could conceivably sanely do it all with one skeleton.