Well, you're sort of asking a meta-question that has as many answers as you choose it to have — kind of like "What's the best way to get to Times Square?" The answers vary and multiply depending on whether you're in Herald Square, Texas or Uzbekistan. 🙂
One short answer: Calibre has the second-best EPUB reader around, temporarily in first place because Thorium has a persistent font-rendering bug. It's also great for converting e-books among six different formats, something that seems to be of paramount importance to some fairly large e-book collector/trader community. Otherwise, it's not really a very good tool/set for anything; even the book-builder crowd doesn't think much of it in that respect.
All of the other answers will depend on your skill set, background, expectations and approach to creating books. There are basically two roads —
The one you seem famiilar with is the long-standing one of using free, community, shareware, cheap and often idiosyncratic tools to "build" ebooks on a structural/file format level, about on a par with "creating" a print book by setting lead type. This is the approach of most of the e-book community, most of whom are amateurs, self-publishers or just at a low skill/budget level. While this "build a bear" approach was once the only way to create e-books, it's obsolete by a decade or more, much like composition via pasting things on blueline board, compared to publication layout in tools like InDesign. You can go there; the tools are free and the community support is insular, plentiful, and will give you as much completely conflicting advice as you can use. Most will go on at great length about how InDesign is a completely terrible tool for creating e-books.
If you're even remotely serious about creating quality e-books, and have the budget and skill set to use InDesign at a journeyman level, then — in my not terribly humble opinion — there is simply no better path than using InDesign, just as it's the premiere tool for creating print and PDF publications.
Put another way, there is only one path to creating a quality book in any medium: with powerful visual composition tools that generate export formats to whatever medium you've chosen. This is true for print; it's true for PDF; it's true for online and web publications... and it's true for EPUB and through EPUB, Kindle. (All other formats are essentially obsolete at this point, although conversion mania continues.)
A book is a book. Learn to write, edit, create and format books as an overall skill set. If the last step is an export to EPUB, it's no different than an export to PDFs for a print vendor.
You don't create books by hand-making your own paper, carving your own type and grunting over a screw-driven letter press... nor by using structural assembly tools to create a digital book.
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