I have a Kindle book with 100,000+ "locations."
The physical editions of this book all have the same page numbering (they just enlarged or shrunk the page). The footnotes often reference page numbers, which are hyperlinked in the Kindle edition. Therefore it is sometimes possible to find a page number in the physical edition by searching for "p297" or such -- if there is a footnote referring to that page. I use the book sometimes in a group context, and it is still annoying if they say "turn to page such-and-such," and I have to ask for some text on the page to search for. Nonetheless, I knew of this limitation before I got an eBook reader. To me the advantages far outweigh the disadvantages for certain applications.
If a publisher has an eBook where page numbers are important (for example, a textbook), it might help for them to include a section at the end with hyperlinks to every page (p1 p2 p3 etc). Then they would show up in a search. If page numbers are a necessity, it seems like PDF is the best option, since it retains the analogue of paper pages.