Properly defragging and cleaning your system registry CAN and WILL definitely make a very noticeable difference to system performance. The registry is a very large and complex place, and having empty registry keys will most certainly have an adverse effect on your system. Microsoft/Windows' tools suck, and so, the built in registry tool, which Windows uses to manage it's registry, sucks as well, and fails to maintain it properly. If your registry becomes cluttered up with too many uninstalled programs, orphaned startup tasks, corrupted drivers, spyware/adware entries, file paths for files that have been moved or deleted and many, many more things, you'll begin to notice a significant decrease in speed. If you fail to keep your registry clean, you WILL certainly notice your PC suddenly crashing, more and more, as your operating system becomes unstable.
It's not a matter of whether or not this will happen to your PC. It's a matter of how much time, or use, it will take before it does. If you don't often install things, or you leave them installed, not moving any files around, and things like that, then you likely don't need your registry cleaned all that often. But if you're like any other average computer user, you download things at least on a bi-daily to weekly basis. Installing updates or new games or removing programs/games for extra space on your drive, copying/pasting files to different places on your drive.. all that jazz. Those people definitely should clean out their registry once in a while. Neglecting an over-cluttered, un-defragged registry will certainly make your OS slow to a crawl, and eventually, stop working or break. Regardless of how good your computer is.