Pretty simply. The wheel or dial on the back always controls the primary function of the mode you're in (ie, if in aperture priority, you just turn it to change aperture, shutter speed in shutter priority). There's an exposure comp button at the bottom of the 4-way controller and if you're in manual mode, it changes to switch the main dial between aperture and shutter speed. When I press the main button inside the 4-way, I have three choices - the default puts it into ISO mode so the wheel controls ISO, the second choice controls the AF area/method, and the third choice controls WB. I rarely get past ISO, but the others are there if I need them. The button on the bottom (below and to the left of the 4-way controller brings up the mode dial with one push, so the mode dial is always one click away. The top button isn't configurable - it brings up the menu to go in and do anything you can't do with the buttons. And the left side of the 4-way controller is the drive button, so its very easy to switch between single shot, continuous, self-timer, etc. Bottom line, I don't have to touch a button to change my primary adjustment in my current mode, ISO is one click away, the mode dial is one click away, exposure comp is one click away, the AF area is two clicks and the WB is three clicks. I don't really find it much different than any of my cameras - on the Panasonic the control wheel controls most things, but you generally have to hit a button to change what it controls - the GH2 and GF1 have slightly more direct ways of doing a couple of things (like bracketing and burst mode), but its only one more click and I don't use those functions often. My most used stuff is as instantly available as on any of my cameras (except for the X100, which has separate dials for aperture, shutter speed, and exposure comp, but a few other well documents bits of confusion).
Its not laid out like any of my other cameras, but they're all specific enough to take a few seconds to reacquaint myself when I first pick 'em up again. The GRD3 has a fairly unique setup too, but I think a really excellent one. None of these cameras get in the way. The only camera I've ever spent much time with that DID cause me interface heartburn was the EPL1, which didn't have ANY sort of dial or wheel and everything had to be controlled by pushing buttons. I could never warm up to that interface. Otherwise, they've all seemed very intuitive to me.
-Ray