The many-button mouse is appealing as way of reducing movements between mouse and keyboard.
But it's even better to just stay on the keyboard and skip the mouse altogether. Mice have to be the number one source of computer-based tendon injury. Fortunately, the standard laptop is relatively "ergonomics".
I'd actually be interested to have the area where my wrists make contact with the keyboard be responsive like a large version of the old Thinkpad "TrackPoint" cursor dot thingy.
The standard laptop is hardly ergonomic. The trackpad and pointing devices are somewhat helpful but the keyboards are all (without exception) terrible for extended typing. You're much better off getting a separate keyboard with the left and right halves of the keyboard angled inward so that hands and arms can remain in alignment.
But in general, I don't see anything keeping a person from holding their hands in alignment over a standard keyboard and typing. Any keyboard does involve small finger movement to hit the different keys, so a can't see how changing key layout changes anything.
Each person has a somewhat different pattern of habitual tension that can interfere with even normally easy activities, so there are many adjustments work well for some but not for others. Mice are a different story in that they require arm movements for simple input, an inherently inefficient setup.
What keeps you from holding your hands in alignment is your torso. It's physically impossible to have your hands square to the keys and yet keep the natural and relaxed line from your elbow to fingertips. The only way to do it would be to squeeze your elbows together in front of your body or compensate with your fingers (curling in your little fingers and stretching out your index fingers), neither option would be comfortable or practical.
What requires that your hands be "square to the keys"? I'm typing now and my fingers are a angle relative to the orientation of the square keys, yet that doesn't stand in the way of my typing. Yes, my smaller fingers are curled slightly more than my index and middle finger but that's not a huge insult to my physiognomy. The human body is actually pretty flexible but moreover, since our fingers are different lengths, it's hard to say there is a "perfect" place on the keyboard for them. Of course, for true alignment, one would want to have one's hand's palm upward but that's not going to happen with current input devices so compromises of one sort or another are necessary.
But it's even better to just stay on the keyboard and skip the mouse altogether. Mice have to be the number one source of computer-based tendon injury. Fortunately, the standard laptop is relatively "ergonomics".