PokerTracker

I run about 6 different databases because I like to do housekeeping in smaller chunks, rather than have a cache update that takes most of a day. Can this cause a significant performance decrease over running just 2? What if I ran 15 databases, should this matter at all?

The more databases you have the more data that must be amalgamated and the more connection processes that must be kept open. If you have a sufficiently powerful computer you will probably not notice a difference, but we have never done internal testing on as many databases as you propose so I cannot say the extent of the performance decrease that you would experience.