The odd thing is, I've found that I use those constructs "naturally" (i.e. when simply writing text in a text-only medium) in pretty much exactly the way Markdown uses them.  _italics_ and *italics* are semantically different (I tend to use the former for titles and such) but are both usually italics in my normal usage.  (There's also /italics/ but that is not very widespread.)  I do tend to use # instead of = for headings but that's kinda stolen (and mutated) from a different variety of non-natural markup.

I suspect that when the dust has settled, it'll turn out that Markdown is pretty much right.  Maybe with some tweaking, but largely it represents (and IIRC was derived from) actual in-the-wild textual usage.