It really depends on your preference. I just bought my first Wacom last week and I got the Small. I'm using it for video editing on Avid as a mouse replacement, which is certainly different from drawing so keep that in mind. At work, I have 3 24-25 inch monitors. I find working on that to be just fine, though it does require a bit of a steady hand. At home I've been working on an older iMac (27 inches) and I find the size of the Wacom to be pretty much perfect. I never wanted to be reaching around on my desk just to go from one side of the screen to another, so I like the small. The tablet itself also takes up quite a bit of desk space as it is, so I definitely wouldn't want to go bigger for my purposes.
That said, if you're drawing in fine detail you may want to go bigger so that your movements are more precise. As a fallback, they do have a Precision mode that zeroes in on a portion of the screen for much finer detailing, if needed. And of course, you can always map the whole "active area" to any portion of the screen you want whenever you need to.
Hope that helps. Your best bet would be to get your hands on a friend's tablet and try it out. It is an expensive tool so you want the right size for you. I got mine at Best Buy, which has a 15-day return policy, just in case I decided I wanted a different size but as it turns out I'm happy with it.
