Are registry entries that are no longer in use and unnecessary (such as those identified by a good registry cleaner), just that . . . unnecessary? Are they just extra baggage and "clutter" in the registry, or can those entries become and/or create problems?
Empty keys and even keys with data in them shouldn't pose any problems if left intact. Unless a program has an update and doesn't use the same type of settings anymore, then there could be a conflict.