display:inline-block is not one of the supported (required) values in ePub 2, so use it at your own risk.
Other than that, by turning a <div> into inline-block, you're basically treating it as a character, so yes, the spacing will be affected and you'd have to tweak a few things.
page-break-inside:avoid, on the other hand, is a required property and value combination. It should be supported and it should work the way you want. Another difference is that it allows a page break if the whole block does not actually fit in a page, while the inline-block does, as far as I know, completely prohibit it, so the block would be clipped. Sadly, I'm afraid many readers ignore this setting, at least in some situations.