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The first thing you're going to have to accept is that every publication is going to need some manual tidy-up on the exported ePub. Quark 9 has only just been released, so I have no idea what the ePub output looks like, but I strongly suspect they will need fixing just as is required in InDesign - there are certain conventions that change between fixed and reflowable formats and I've yet to see any automatic conversion system that actually gets the css more than halfway right. InDesign has been doing ePub export since CS3 and still doesn't really have it right, so I don't know what Quark's first attempt will look like.
Avoid fixed-layout like the plague. It involves a lot of work that only benefits one platform, and there's no guarantee it won't break in unpredictable ways when Apple finally brings out the fabled hi-def iPad. CSS 2 is a bit limited, but it offers a reasonable set of tools to handle positioning. This will be more difficult on the Kindle, though.
As far as landscape vs portrait goes, it really depends on the design and how much it's going to be compromised by forcing it to flip. If the photos in your series are predominantly landscape, then the quality is going to suffer even more by forcing them to be displayed across the shortest dimension. None of the current readers compares to print when it comes to resolution, so you want to make the maximum use of the pixels on the screen. The Kindle and ADE-based ePub readers can switch to landscape easily.
I suppose one thing you'll also want to consider is whether you really want to stick with Quark and whether it's worth investing further in their platform, since there are ways available to transition to InDesign. But that's quite a big question that would need to involve the whole company.
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