I chose the Kindle because it felt good in my hands and was easy on the eyes. ePub is the universal format, but that hasn't stopped me from being able to read anything on my Kindle. The format converter within
Calibre is quite good.
Even DRM isn't an issue, depending on your ethical principles. My sister gave me a gift card to Barnes & Noble. I have every intention of purchasing some e-books there, in all their DRM-wrapped, ePub glory. I'll install a DRM-stripping tool, followed by Calibre seamlessly converting the books to Kindle's format as it sends them to my device.
Because of the format flexibility, I'd suggest making the physical ease-of-use your highest priority, followed by your GUI preferences. Or vice-versa. Try some different e-readers. Talk your friends into letting you use theirs for a few hours. Try a Nook at a Barnes & Noble store. Unlike Beta vs. VHS, the e-book format is actually a minor consideration IMHO.