I have the 350, Nook Color and Kindle 3. I've owned the 900, Nook and briefly the 650. Of ALL of them the 350 is my favorite. Being able to slip it in your pocket is a great benefit. The size is perfect for me when reading in bed..much nicer to hold onto than any of the other devices. I read one handed and use my thumb to swipe on the screen to turn pages. One thing to know is that a "swipe" doesn't have to be very big, .25 inch of movement is all I do to turn pages...easily done holding the 350 one handed.
The Nook color is nice, but I use it only to surf the web and watch movies. It is not nearly as nice to read a book on as the Sony. The Kindle has sort of become the least used. I love the device, think it's really well designed, but it's not comfortable to hold, I accidentally hit the page turn buttons sometimes and the web browser has been eclipsed by the web browser in the nook color. Sooo...the kindle does many things ok, but nothing excellently.
Back to your original question, I find the screen size and readability of the 350 perfect. FYI I'm 46 and have the typical vision issues (and more) of a 46 year old..