(1) Some forms of "2.5D" are very doable in Spine, though how hard it is to do depends on what you are planning to do.
You can check the showcase forum: viewforum.php?f=5
This spine-users blog: http://spine-users.tumblr.com/
And the showcase hashtag page: #madewithspine
You'll see samples of some people doing that.
Particularly:
Zodiac Orcanon Odyssey, Spine showreel. - YouTube
Zodiac Orcanon Odyssey, making of Temple Statue Boss on Spine. - YouTube
girl - YouTube
stb - YouTube
To quickly try it out yourself just in the editor, you may want to try rigging something simple. Note that the trial version can't save so I don't recommend spending time making anything you'll get attached to.
(2) Regarding size on screen: Not specific to Spine. Look up "GPU texture fill rate". The more area of the screen your images or meshes take up, the more of the fill rate it consumes.
Regarding number of parts: that may be something you need to test yourself, especially with the unusual build pipeline. The intervening translation from js to various target platforms may incur a performance cost that's possibly not ideal for graphics-intensive games. If that's been shown to not be a problem, then you should have no problem using Spine either.
(4) I don't think we've done benchmarks yet. But between the two, Canvas is not ideal if you're looking for performance and full features. WebGL is the way to go if those are your only two options. Canvas is probably best for simple animated elements on webpages, even then, some cases are better handled with WebGL.
(5) Not specific to Spine. Look up "GPU maximum texture size". Particularly, look up the ideal/maximum texture dimensions for the devices you're targeting.
Nothing about this seems to be NSFW. I'm not sure why it was even relevant to mention what you were planning to make.
Just don't post any images though. You may get banned.