Master Phruby

That depends on how busy it is, and on the applications using it.

Kinda depends who's asking. If it's a client, you'll need many hours a day including overtime. If it's for fun/yourself, yeah, just set it and forget it! Make backups. 

Running - not so hard.  Performance might be a different story.

MySQL is probably a little bit easier than MS SQL, but if you want to fhck with any database system, just go changing data on a massive scale and see what happens.  If you update 70% of the rows (or insert or delete) you will likely get some unexpected behavior, but I'd stop short of saying that it would stop "running."  Of course, if you were to delete a table critical to a specific application, well that makes for an exciting Friday morning.