First a disclaimer: I am not a touch typist (yet). So my thoughts on typing flow may be WAY off base. Please correct me if I stray.
In the never ending search for the holy grail of keyboard layouts, I have found that many designers may be over-rating letter frequency. Surely its important. The top 8 letters (ARSTNEIO) probably DO deserve to be on the home positions, but we may be taking this criteria a bit too far. There are many criteria to consider, as Shai and many others like to point out, such as hotkey placement, similarity to qwerty, aesthetics and symmetry. Also a big one is typing flow.
Typing flow can be broken down to smaller aspects like same finger, row jumping, hand alteration. etc. But what I never see mentioned are breaks/pauses. For instance, I and everyone I have watched seem to type in sort of chunks or bursts interspersed with slight pauses. I'm only talking fractions of a second here, but its very obvious when watching a poor typist. It is true that the actual bursts may be taken into account when we talk about digraphs and trigraphs but what of the pauses. And what of how the pauses interrelate to the keystrokes before and after.
Lets take a look at the space. Does that space represent a break in thought, hence a break in flow? And is that break long enough (or perhaps 'natural' enough) to allow your fingers to return to their home positions if the previous key was an awkward stretch?
Heres an example. The comma and period are almost always followed by a space. Lets say we put the comma on the B key(probably the worst stretch in the main keyblock). When I hit the B key, my whole left hand except for the pinky move out of position. Having a comma there almost ensures that the next keystroke be a space and might allow enough of a pause for your fingers to return to get ready for the start of the next burst. Now the comma is the most frequent punctuation mark, and if looking only at frequency, it deserves a better key position.
Things get trickier when talking of shorter breaks, like the end of trigraphs. Look at the word 'tethering'. First off, what are the bursts? They are probably different for everyone. One might type 'te'the'r'ing'. And someone else might type 'tet'her'ing'. The (') indicating the, lets call it, micro-pauses. Also, a single person may type it both ways just depending on how much sleep he got the night before. I find that my bursts tend to follow the syllables of a word, but are rarely longer than 3 letters.
I'm probably looking at this all wrong. Maybe a good typists flow is more like a musical beat or rythym and only the poor typists start/stop in bursts.