Interesting article, Jeff, thanks for sharing.

Six years ago, when CommentPress was being revamped, we went a fair way down the road of attempting multi-theme compatibility for marginal commentary. We decided against it in the end, because of the difficulty in determining a theme's structure and layout. As you say, it really is difficult. We also made a deliberate decision that commentary and text should be easily readable together, which is why CommentPress has a couple of bundled parent themes where comments are shown side-by-side with the text.

In my view, the major roadblock to a multi-theme approach is that it requires Javascript-based DOM manipulation. Digress.it, which forked from CommentPress back then, took the JS-led approach. CommentPress, on the other hand, works with Javascript disabled and is thus fully accessible out-of-the-box and functional on screen readers, whose Javascript capabilities are often limited or non-existent.

There a other, more subtle complexities that the JS approach may struggle with. Consider the comment permalink, for example: I can see no way to share a link to a comment on:
http://www.strategio.fr/projet/wp-side-comments/
In CommentPress, comment permalinks just work. Here's a link to a comment on a page:
http://futureofthebook.org/commentpress/#comment-77711
And here's one to a comment on a multi-page post created with the quicktag:
http://futureofthebook.org/commentpress/a-multipage-post/2/#comment-88062

Another problematic example: what happens when you print your page? In CommentPress, although the comments are no longer marginal, they are listed by paragraph below the text. Try print-previewing any page on the CommentPress site to see this.

In addition, a Javascript-based approach not only make theme compatibility difficult, it makes plugin compatibility equally difficult. The CommentPress approach makes it compatible with BuddyPress activity streams, enabling more architectural integration with WordPress to achieve social peer-review systems and class-based commenting such as:
http://commons.digitalthoreau.org/walden/

In the end, I agree wholeheartedly with Nick Haskins when he says "There comes a point where just has to be in a theme, or in an ecosystem around said plugin." This is exactly the CommentPress approach.