I wholeheartedly recommend the excellent Kinesis Advantage 2. It's relatively expensive for a keyboard, but absolutely worth the money for anyone who uses a keyboard professionally for hours every day. It also has featureful firmware and the ability to remap keys in hardware. I wish I had purchased one years ago. My typing is faster and feels like much less effort.
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.
I wish these good split keyboards had staggered rows like a regular keyboard instead of a grid layout. I have an Ergodox and couldn't get used to the grid.
I know Kinesis has other split keyboards but they don't have mech switches.
