I try to answer you according to my experience: I have a Cybook Gen3 (6") and a Cybook Opus (5"), and I've been two years reading in a Palm.
For the people that own both 5" and 6" devices and have bought them
both for personal use:- Which one did you buy first, why did you buy the second device?
I bought first the Gen3 and later the Opus because I prefer the portability (I buy my bags according to the device I use to read and I can't buy big bags because of my back).
For those of you who own a 5" device:- Is the screen big enough to read comfortably from?
Yes, of course, I've been reading at a Palm after all 
- Do you find yourself pressing the "next page" button too frequently?
Define "too frequently". See answer before.
- How does the reading experience compare with reading from a normal sized pocket book.
Measuring one, I noticed that a 5" screen would show14 lines less text (37 lines) than the measured pocket book 51 lines (small text in this book). As this text is rather small, I'd have to make the font a bit bigger and thus loose a few more lines. Adding one inch would ad about 8 more lines in this example.
Better, the reader weights less. Sorry but I don't count lines, I read.
What about the size of the whole device from a ergonomic perspective?- Is it comfortable to hold (most devices seem to have roughly the same shape, but lets skip page turning here since this can be too different from one device to another) for a longer session?
Well, I've been reading about two hours or more without problem, so I think it's comfortable.
- How do you hold the device while reading? (Bonus: 5" vs 6"?).
In this, 5" is better than 6". 6" device, I can't get it with a hand, 5" yes. So, for traveling Opus is better for me because I can rotate 180% and hold it with left or right hand depending on how I hold myself.