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If you want to make paragraphs, I think the right thing is <p>. <span>can be used for some special characteristics, not in general, as I've seen. And <div>, well, I think you can do it very well without them. I you use <p> and <h?> for chapters, you can obtain quite a good format and, with css, you can change all the characteristics you want for these tags (I've done it and works quite nicely).
I don't know about MOBI/ePub formats difference but with very simple tags you can make a very good e-book.
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