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Epub is basically a zip archive. If it's DRM-free, open it with WinRAR, 7-Zip, etc., and replace de JPG image (with the same filename, resolution, etc).
If it's PDF we're talking about you can have a look at my signature. Simply delete the cover page (usually the first one) using Adobe Acrobat X (or whatever) and add the one from Inkscape, or replace it entirely.
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