Interesting question "How safe is the Safe ?"
I travel quite a lot for my job and have been to LOS 10 times so far, so here's what I have found out and do.
* I have never had any problems with leaving cards, cash etc in the safety boxes in a hotel reception.
* I always look for hotels with an "in-room" safe, but safety boxes in reception will be fine if I like the look of the hotel.
* I always carry 2 credit cards with me. As soon as I arrive, I use one to take out some money to get me started. Once this is done, I put both cards in the safe.
* Before leaving home, I advise both credit card companies of my travel itinerary so they know to expect transactions from those countries I am visiting. I also check with them what numbers I should use in case of emergency (they do change, so don't rely on old statements etc. for this info).
* I take a photo-copy of my passport with me and carry it in a small plastic holder inside my wallet. The holder is one that is normally associated with tube/rail season tickets and is given out with the ticket as a holder for it.
* The passport plus any cash I might have brought with me goes in to the safe as soon as I arrive, along with my air-ticket home.
* If you have an in-room safe, use a number (some allow use of a card with a magnetic stripe as well) that you know you will never forget. For example, you mother's birthday in number format i.e. 10th of April would be "1004".
* Never use your credit card PIN number as your safe number
* If your "in-room" safe is one of the older kind, (insertable lock and key) always check what the cost is if you lose the key and make sure they have a "spare" - you may laugh but some don't keep spares and they use a locksmith to open the safe if you lose the key
* If you have close family at home, give them brief details of anything that you might need to know, should the worst ever happen, i.e. everything goes. For example, leave an envelope with them that has details inside, like your passport number and expiry date, your credit card numbers and their emergency contact numbers, the airline ticket reference and contact number for airline, the number of your Embassy (for me it would be British Embassy in Bangkok).
The last one hopefully you will never need and as I said, is in case everything goes for whatever reason. I leave my "envelope" with my mum (bless her) and it means that I can speed up any process by having all the relevant details available to me by virtue of a phone call to home.
I'm sorry if reading all this makes it sound even more frightening, but until you are ever in the position where something has been stolen or gone missing, then you won't really appreciate how much these steps will help eliminate. I hope it never happens and you have a safe trip, but "it's better to be safe than sorry".
Good luck