I'm wondering...
Under the assumption that the thief goes after "easy" targets, first, would it be such a bad idea to simply put a paper sticker across the room safe with one's signature on it? All that would do would provide evidence of tampering, however it might deter the amateur hotel employee thief. Such a person would enter the room prepared to open the safe, not peel off and somehow replace a paper sticker. (You might want to travel with a small bottle of WD-40, which is great for adhesive removal.)
Having said that, I have always heard that truly valuable stuff should go in the front desk safe. The manager on duty is the only person with access to the front desk safe, as far as I have always heard. I don't travel with the Hope Diamond, so haven't had a great need for super-secure safes. The only thing I ever leave is my home cell phone, house keys, etc.