I have testing thumb cluster layouts and have come up with a nice combination for my own thumbs. Reverse the keycap on the "front" key of each pair so the thumb rests nicely on both (I am using lower row caps). This way you can press either one by rocking the thumb forward and back and you can press both together easily.
Left thumb: front button = Shift, back button = AltGr
right thumb: front button = Space, back button = Enter
Then I have another pair of keys for each thumb next to the first (more outwards):
Left thumb: front = backspace, back = Tab
Right thumb: front = Alt, back = Ctrl
So you can press any combination of Ctrl, Alt, Shift and AltGr.
I placed them like this so the most used keys are front inside buttons (shift and space). Modifers together (AltGr and Shift, Ctrl and Alt). And other most used "little finger" keys on other buttons (backspace, enter, tab).
Of course this requires a complete keyboard design... I am working on it
Using a Teensy 2.0 so I can code my own firmware, no modifier limitations, etc. Currently testing thumb cluster placement and angle. I may start a thread