Nikon did a substantial redesign on the D4 to streamline operation, especially for video and vertical shooting.
Large, but comfortable
Though it doesn't look particularly large in the hands of Steve Heiner, senior technical manager at Nikon, the D4 is about the same size as the D3S. It feels lighter, however, with a smoother, shinier metal surface that's popped up on a couple of new cameras I've seen recently, like the Canon G1 X.
Nikon redesigned the shoulder of the camera, with an increased angle and a dial tilted slightly upward (so your finger doesn't drag on the red rubber decoration). It also has a direct-record button, in support of the D4's enhanced video capabilities.
Though the consistency is necessary for longtime Nikon pro shooters, I've never been crazy about this controller. I don't like having an important, frequently used control like metering under my left thumb. The button lock mechanism for the burst mode dial has always been a relatively elegant design, though.
The D4 has a lot more controls on the back than the D3S, in part because many are duplicated for use with the vertical grip (as has become common in this class). There's a new joystick--two, actually--and a dedicated Live View switch. For the AF area mode, the D4 uses the same convention as the D7000, with a button on the focus-mode switch (on the front of the body to the left of the lens) that brings up the AF-area mode options.