Bigger ones allow you finer control, since your hand moves a smaller distance. You need space on your desktop though.
I use the 6×9. The 9×12 is nice, but too big for this desk.
I like to use a mouse sometimes, especially for video editing, where precise double-clicking is necessary. Sometimes double-tapping with the pen causes things to move if the pen slips.
I’ve found that they work well with double monitors, but I don’t know if they will work well with all systems. I used one with a double-monitor PC setup in 1998. I would Google “wacom” and your graphics card, or e-mail Wacom to make sure.