I reckon reStructuredText is the best syntactic and semantic foundation of all the ones I’ve seen, but there are a few things it could do with changing. Most significantly, reStructuredText is designed for being written in a sane text editor, where indenting stuff is easy; but this doesn’t work well for use in a plain <textarea> as web applications of it will commonly go for, where any indentation must be applied manually by the writer. So I’d say it’d be good to get a new syntax construct for fenced, rather than indented, directives. For example, this is what reStructuredText has:

  .. directive-name:: first-line-options
     :subsequent-options: and their values
     :and-more: if you want

     Then the directive’s body.

And here’s a strawman fenced syntax:

  ```directive-name:: first-line-options
  :subsequent-options: and their values
  :and-more: if you want

  Then the directive’s body.
  ```

Of course, once you’re touching something like that you’d want to touch more things to make it all consistent again, but it’d all be perfectly possible. (Would you use backtick? Dunno. I hear it’s hard to access on some keyboard layouts like German.)

As it stands, reStructuredText is based around having visually-pretty source: monospacedly-aligned tables, indentation for hierarchy, that sort of thing. (Headings feel like the only major thing that doesn’t use very significant whitespace.) I almost always like this, but there are definitely some situations when it’d be nice not to work that way.

Would you go all-in on fenced things rather than indented things? I dunno. Probably.