A few thoughts on this topic:
1) I have certainly seen surcharges on my bill for the in-room safe. These seem to be much less common today than a few years ago, though I'm not certain to what extent that's because industry practices have shifted versus changes in brands and locations of hotels I've typically stayed at.
2) In over 1,000 hotel nights in recent years I have never had anything stolen from my room despite rarely using in-room safes.
3) I believe housekeeping and other hotel staff are, by and large, honest. Moreover, I believe most those who might be tempted to steal realize that they would automatically be the first suspected in the event of a guest reporting a theft.