I've tried it. In portrait mode, my old 24" 16:10 monitor is already tall enough to wreck my neck and be really uncomfortable to read. I wouldn't even want to try that with my current 27" 16:9 monitor..
Just how close to your monitor do you sit? I have no problems with my 24" 16:10.
The nuisance for me is actually rotating the monitor, particularly if OS support for detecting such and automatically rotating the view is missing. So while I like portrait mode, I tend to just keep it one way or the other, based on my overall monitor configuration.
I've tried it. In portrait mode, my old 24" 16:10 monitor is already tall enough to wreck my neck and be really uncomfortable to read. I wouldn't even want to try that with my current 27" 16:9 monitor..