The Advantage layout is definitely one that sort of insists on two hands if you want to reach anything that the right hand types regularly and/or you want to use the arrow keys. The keywells are open on the outside edge, so it is pretty easy to slide one's hand over onto a mouse or trackball, but I agree that a conventional layout has at least some advantage there (I think a split keyboard would fall somewhere in the middle).

I don't find it to be much of an issue in practice, because I use the Advantage 2 along with a CST L-Trac trackball, which sits right beside the keyboard and can be operated with just a couple of fingers. They have a model which can accept external buttons, which is the one I got, so I also have duplicated the LMB and RMB next to the other side of the keyboard. In this way I could theoretically use the cursor with my left pinky and click with the right pinky without taking my hands off the keyboard, although it's not particularly effective (or necessary).

FWIW I am someone who uses mouse-driven interfaces all the time, although I guess emacs more than makes up for it with the amount of keyboard activity it demands.

Kineses also has something called the Freestyle, which you might consider looking at. I have one for work and one for home.