I currently own a Nook, PRS-300 and PRS-600. Eventually I'll narrow down to one device (see my signature)
The 300 really is a joy to use - it's perfect for one hand, either hand. I don't notice any issues with fast reading, and the screen is sharp and beautiful. My only complaint IS the storage size, since I am a re-reader with many ebooks to organize and store. I really wish the 300 had a SD card slot. The page refresh is a touch slower than the 600, but I get into a rhytym of hitting the page forward button at about the second last line, and I'm fine.
The Nook is also fabulous for one-hand use with the buttons. I can read one-handed with it for a shorter period of time (15-20 min), but my wrists and elbow get fatigued if I use it too long. I have partially solved that problem with the Industriell easel cover, although it doesn't balance on the bed all that well. And I'm still searching for a decent book light that doesn't blind me (Sony really has spoiled me with their great light case for the PRS-600).
Office Max has the PRS-300 on open display so you can pick it up and move it around, and B&N has Nook out. Both are tethered, but you still get a feel for their ergonomics.