For multitouch devotees, the addition of gestures should feel seamless, but I have to admit that touch interfaces have always felt awkward to me when I'm not directly operating on the screen. That said, I rarely experienced what I thought would be the biggest issue: confusion between the signals from the pen and accidental hand swipes. When operating wirelessly, though, I did feel like there was a slight operational lag that I didn't experience with a pen or a mouse.
Oddly, the thing that took most getting used to is the new surface of the active tablet area, which has a slightly rougher texture than the Intuos4's (most likely for better touch response). But after a few days I had either adapted or simply worn it down a little. It probably says more about me than I'd like, but the membrane keys really appeal simply because they don't have cracks for food and schmutz to accumulate. Plus they have various bumps embedded for easier identification by feel, something I'd complained about in the Intuos4. And in case you were wondering, it doesn't supply touch pressure sensitivity or any finger-based drawing; you can paint dots by tapping with a brush tool, but finger painting isn't on the agenda. Finally, its inability to share the driver customizations and settings between systems remains a major annoyance.
For graphics, the Intuos5 doesn't advance over the Intuos4, but it's a lot more flexible than its predecessor if you want to use it as your only input device without losing the top-notch sensitivity.