"safe" is not how i would describe it, but I would say the risk of total failure is very remote.

On my system, Entourage is hard shutoff (crashes, power outages, force quits) probably a dozen times a year or more. Since I have had office 2004, I have only had entourage complain once about problems, which were fixed when i rebuilt the database (by holding the option key down). All and all I would call it's databasing system fairly robust.

in practice, I rarely ever have a NEED to recover from a backup, because I dont have system failure often. In the event that I do need to recover, odds are even if the backup occurred during a database update I will be fine. If I am not fine, I will rebuild the database, and if that doesn't work, there are hundreds of other points in history I can try.

If I were planning to migrate to a new hard drive using time machine, I would absolutely shut down entourage first, then do a backup, then do the migration. The rest of the time, I feel that the risk of catastrophic failure doesn't even exist next to the possibility that I can have incremental backups of my 4GB mail archive.