This FAQ may help, especially if you are using Zone Alarm or similar:
Registration Certificate suddenly expires or does not stick
If that doesn't cover it then it sounds like something is blocking Opus from writing the certificate file. It could be a "security" program such as Zone Alarm doing something stupid, or it could be that the file permissions on your HDD have been changed by something to prevent your account from being able to write to where Opus stores its certificate. If all else fails, Process Monitor can be a good way to track down exactly which operation is failing, and on which file or directory.
If none of that helps please let us know what the full error message is.