One of the key reasons I developed RegBench was to see what effect registry defragmentation and cleaning really has on its performance. In theory, it should make a difference, as more optimized registry hives results in quicker traversing through its data structures. However, in practice, it could be that only in extreme situations does the registry hive ever get to a state that severely diminishes system performance. That said, if it isn't the registry, then what does cause the performance degradation we all see with Windows over time? Shell extensions, more programs running, IE add-ons? I dunno, please report any findings you do have.
What we need is a system in 'bad shape', run some RegBench benchmarks and get consistent results, then try cleaning and defragmentation, then re-run the benchmarks in the same system state (or as close as possible, no apps running, etc..).
Also, we must be careful, as the current RegBench consumes a lot of virtual memory, so it may need code modification so that it doesn't end up benchmarking the performance of page swaps (VM pages in and out) instead of the registry ;o. You may try benchmarking the HKCU hive instead of HKLM, to help reduce VM usage in this current version. I will do what I can to reduce memory usage soon.