This is actually the trickiest part for me to determine. I've conjured over the idea of shoulder buttons "to stride" with my controllers for points where I absolutely cannot make a mistake as to left or right but I don't find the d-pad particularly lacking so it's unnecessary.
For controllers my current theory is that you want the base joint of your thumb handling constant actions and the top of your thumb handling less frequent reactionary movements. This is in mostly because the top portion of your thumb is a further out extremity and has a wider range of motion but also because I think curling is more natural starting from base to extremity.
The D-pad is always movement. That's what it's for.
With a diamond layout using south to fire, west to shoot and north to bomb seems to work nicely. This is because you're always firing with the base of your thumb, a slight tip of the thumb focuses. Bombing seems kinda hard to pull off because it requires a slight movement but having it in north position is better than south because when you hold out your palm, it's more natural for the thumb to move closer to the fingers than away from them. This means an upwards motion on the controller should be a little easier because it goes more towards my other fingers with a traditional grip.
If I'm using shoulder buttons L will usually be my bomb so each hand only has two responsibilities at any given time. Left hand bombs and moves, right hand focuses and shoots. Less often I'll set focus to R.
With a genesis six button layout I'm guessing perhaps you could position the hand at an other angle so your thumb lays across three buttons flat and use C to fire, B to focus and A to bomb. I haven't done this myself but it matches up with the extremity curl theory quite interestingly, although with my Nubytech controller the grip is rather noticeably tightened, so I'm not sure about the long term sustainability. I'll have to try it sometime.
With the joystick deciding is a bit simpler. Again it's obvious what you want to move with so you just have to decide upon the buttons. From left to right, focus, fire and bomb is the order they appear on the default layout on the keyboard, although I like to mirror it for use with my opposite hand. Which three buttons I use is a bit trickier to decide. I'm preferring the top row for whatever bizarre reason but the T.E. stick still gives you four buttons to choose from. The three on the left make use of the offset button while the three on the right are perfectly aligned. I'm using the right ones more often but the left isn't without appeal either. Either way the button hand eventually starts to hurt, same as with the keyboard and I'm not sure why this happens.
Also it's probably not something most consider but I prefer my pause button being on the top of the joystick as opposed to the back, since easier access means faster access which in turn means pausing is a less disruptive action. This'll usually make me use the button on the opposite polarity of my edge-most button. However on the PS3 edition of the stick, the home button works nicely for this purpose because it's out of the way and Windows doesn't know what to do with it. On the 360 edition the equivalent button has a reserved function as the identifier in Windows, which is rather actually a bit of a shame considering that this is the perfect spot for a miscellaneous action.
