The complete Wii control setup is weird. You have these two one-hand gadgets connected by a fairly short cord, which makes the notion that it's wireless a bit of a deception. I've smacked myself in the face with that cable too, so it's far from unobtrusive. Also, having the two halves split apart takes away a lot of the stability that comes with something you hold firmly in both hands. After a while, I'm holding the nunchuk in a weird position, with my wrist tight against my ribs for longterm support. I relax when I think about it, but later, there I am again, with the stick jutting out to the left instead of up, held in tight against me. I do something similar with the remote in my right hand. Pointing is a lot more stable with the wrist against the ribs, and I can hold it like that all day. Only some things require violent enough motions to mimic real life. Most of the time, short gentle gestures will do.
It's a lot to get used to, and hopefully, something to design better next time around. For one thing, the button layout on the remote is atrocious. Only A, B and if I'm charitable, D-pad-down are in any way ergonomic when holding the remote the normal way. The problem is that even adding C and Z on the nunchuk, these are not enough buttons to do all there needs to be done during involved action games. As a result, you need to contort your thumb, slide it down uncomfortably and far, to reach the other 4 usable buttons, namely plus, minus, 1 and 2. Plus and minus are these tiny buttons on either side of the Home button, which although recessed, can still get pressed by accident when stabbing blindly at one of the others. That's like the big round button on the 360 controller. It brings up the Home system menu, completely taking you out of the game until you cancel out. 1 and 2 are much further out of the way, but at least those are big buttons. Providing you have a flexible hand and a good reach, it can be managed. But it shouldn't be. Either these buttons should all be duplicated in a place that makes sense for holding the remote normally, or they should be entirely new well-placed buttons. A third party should really run with this ball. Nintendo didn't carry it far enough.
All these observations come courtesy of my experience so far with Metroid Prime 3: Corruption. I already laid out the bad news. The good news is that Retro did a great job with the strengths of these controllers. The weaknesses could not be avoided. Anyone who played the earlier Primes knows how many different things need to be controlled adequately. Retro had no choice but to use all the buttons, however awkwardly placed they may be. But the meat of the action could not have been handled much better. Using the pointer for looking is second best only to mouselook, and it's actually more intuitive (but less practical). There are 3 different "sensitivity" options for how the screen reacts to pointer input, from the so-called Red Steel method everyone hates (push the screen when the cursor gets to the edge) to the terrific "Advanced" setting, where the further the aiming reticle gets from the screen center, the faster the view moves in that direction. Motion is with the analog stick on the nunchuk. It works very well, and after getting used to it all, it becomes second nature, just like mouselook does.
By default, A shoots and B (trigger) jumps, but I thought this was exactly backward. I got a gun, let me shoot it with the trigger. Jumping with my thumb (A) is what I've always done. Fortunately, you can invert the default controls. This all feels perfect after a while. Missiles are fired with D-down, which is less than perfect, but works. Z (nunchuk trigger) locks on enemies or freezes the current view if there's nothing to lock on. C (button on nunchuk) rolls you up into the morph ball. That's as far as the rightness goes. For everything else, you need practice reaching for the stupid out-of-the-way buttons and no arthritis. Somebody come up with a right-hand controller for MP3, please. The game deserves it.
Edit: I forgot one important detail: You cast the grappling hook with the nunchuk, and yank back on it to pull things off or apart. These motions feel very natural. It's another good use of the technology.
Also, there are times you use the remote to push, pull and turn (twist) devices in the game world. Very neat.