All of that customizability is expected, perhaps, but Razer also includes some extra features with the Naga Epic to help you get acclimated to using so many buttons.
One of the chief difficulties we encountered was knowing which buttons our thumb was actually touching. You can figure out the row you're on easily enough, but it can be hard to determine which button you're on within each row based simply on touch. The buttons in two of the four columns have raised ridges to help provide some tactile differentiation, but we found that wasn't enough of an indicator. To solve this problem, Razer includes a sheet of adhesive gummy dots you can use to give your thumb an anchor point. You get 12 dots in the box, but we found that even one dot positioned on a key in the middle of the pad helped us keep our bearings.
The other problem we had using the Naga Epic is remembering which key did what, and training ourselves to activate that button on the mouse as opposed to the keyboard or via the onscreen cursor. We can imagine this getting easier with extended practice, but we also expect that you will come to use some of the buttons more than others, based on the convenience of their position and their overall utility. We should also add that in addition to gamers, design pros often rely on a large number of macros and keyboard shortcuts, and we can imagine them using the Naga Epic to help streamline their workflow.
We can forgive a learning curve in a mouse, but it's a bit harder for us to justify the cost of the Naga Epic. For just $20 more, the Mad Catz Cyborg R.A.T. 9 provides a wireless gaming mouse with the same 5,600dpi sensor, as well as a weight kit, and far more physical customizability. Granted, the R.A.T. 9 doesn't have the thumb-side keypad, but its features come across as far more useful and less gimmicky. We especially appreciate the weight kit and the hefty build of the R.A.T. 9 in general. The Naga Epic has a nice shape to it, but it feels very lightweight.
From a more cosmetic point of view, the Naga Epic also features LED lighting that shines through the keypad numbers, the scroll wheel, and the logo underneath the wrist rest. You can even use Razer's configuration software to pick from 16 million different colors for the LED. The R.A.T. 9 doesn't have that kind of lighting, either, but then we'd also guess that rarely has an LED contributed to faster damage output or a higher kill rating.