I need to move the main Windows folder (About 22Gb) off it's current hard drive and onto another one. Is it as simple as copy and paste while the computer is running and booted up? (I'm guessing it's not, but I'd love it if it was!!!)
Unfortunately, it's not. Judging by your Windows' folder's size I assume you're running Vista or newer. On those operating systems Windows massively relies on hard links. Copying the folder like you plan to would destroy them and probably introduce a plethora of problems.
Also, there are folder and file access rights that will prevent you even touching most of the content. You could probably copy the folder. You weren't really clear in your question as to what your goal is. Do you just want to move the files and have them ready someplace else, or do you actually plan to have the system fully functional and bootable on another hard drive.
I assume the latter and it won't work the way you have planned. You'll need imaging software for that. Image your hard drive and restore the image to a different hard drive.