If HTML/CSS (or more specifically, some HTML renderer) had somewhat better support for paragraph-level typography and column-by-column or page-by-page layout (that is, hyphenation, justification with proper paragraph composition, widow/orphan controls, better floating image positioning especially in a multi-column context, some ability to organize floating content both horizontally and vertically without using tables, page numbering and same-page footnote layout, etc.), then it would be a perfectly fine e-book format (or, for that matter, printed book format). Adding support for all the typographic features in modern fonts (small caps, uncommon ligatures, lower-case numbers, etc.) would be a nice plus, but wouldn't really be essential.
Unfortunately, as it is, the book printers of the 16th century were able to make more readable text layouts than can be easily done with HTML/CSS today. Instead, all the new HTML/CSS features are focused on whiz-bang, rather than getting the (text) basics right.