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Photo, or image, heavy books are a pain. Fixed layouts ePUB is limited to iPad (iBooks?), so that won't help on the Nook and Kindle. Furthermore, the Kindle does not accept ePUB at all.
Since ePUB is based on XHTML, it is a flowing format by nature. This will of course give issues when there are pictures in the book. Large free spaces will occur. Mobi also uses HTML, but I am no expert regarding mobi.
Personally if I would have to make an image heavy book, I would go for PDF. I know the limits, but I feel that unfortunately it is still the best format for it. Most readers support PDF in one way or another. The small screen could render the PDF hard to read. You might want to test with different page sizes to come up with a compromise that is acceptable on multiple readers.
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