1. If you want to review/analyse all of your data in PokerTracker 4 reports then you would need to use one database - only the HUD can read from multiple databases. The advantage of multiple databases is that they are easier to manage if you have to do some housekeeping at some point and you delete databases you don't need anymore without having to purge hands from one big database or starting a new database and reimporting hands.
2. I am not sure what you mean but it is ideal to have as much free space as the size of your largest database, although for most operations that much isn't really necessary but it will be required for things like cache rebuilds.
3. Performance depends on many factors and I couldn't comment on that but to create databases on another disk you will need refer to
this post in a different thread of yours. If you create databases on another drive then you can still have the HUD read from those database(s).