It depends on your method of updating. If you use the Launcher to update to 3.50.033, you can go straight from 3.00.366 (or any other version, for that matter). If you download the standalone update from RealFlight.com, you will need to have version .448 first. Otherwise, as Travis mentioned, you may be missing certain data, and that could manifest itself in very bizarre ways that are difficult to track down, making you think something's wrong with the program when in fact it wasn't updated properly.
Contact RealFlight tech support for assistance if you need to download the update. They can help you get from .366-->.448 first. I'll tell you up front that using the Launcher, if at all possible, will be a much simpler and more straightforward process.