> To reiterate, for me it seems that itunes and ebook reader generation of devices and applications don't seem to value custom directory organization.

Yes, because it's expensive and has little value for the user. A guided application, streamlinend for well defined purpose is always simpler to create and cheaper to maintain. There is a reason why free software is usually more open for user-custimization.

> While the library part of calibre is very good, the reader part is not so great

Indeed. I thinks it's mainly because calibre is mostly used for feeding devices and maintaining and manipulating the library, less for actual reading books on desktop-PCs.