Sarah,
Other than the image size issues, there's not a huge amount you can do, though perhaps you can fit a separate CSS/style-sheet for different devices though that'll likely lead you down the road of insanity ultimately as well.
We've found, the less you mess with it the better it works out.
For the images, you might try go with setting its width in the style based on page-width or similar, rather than absolute pixels. Of course, this is no guarantee, especially if the ereader doesn't support image scaling.
Wish you the best of luck.
Paul.
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