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I don't read any books using calibre. I may check the title pages and the cover quickly, and verify that the book opens, but that is usually all. Sometimes I also do some light editing, but not often.
I do most of my reading using an Android tablet and the Mantano Premium e-reader app. I think it handles both ePubs and PDFs beautifully. I convert all other formats to ePub before I send to my device. One of the strongest features with calibre is the ability to convert between formats. I don't convert PDFs. PDFs don't convert well.
To simplify things I would recommend that you only use two formats. PDF is given, since it doesn't convert well. Then I suggest ePub, since that is the format that calibre handles best, and also easily can convert to any other format. But if you have some e-reader device, then you most likely should use a format that device supports.
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