For a full-time traveler, it can be difficult to keep valuables out of your checked bags. Since I'm on the road about 10 months per year, my checked luggage carries most of my clothes, personal items and effects; however, I make a point to stuff my most valuable possessions into my carry-on. Then, I don't let my carry-on out of my sight.
It doesn't matter if you use TSA-approved locks on your bags. I've used locks and twist-ties on my bags, and still had my luggage searched thoroughly when traveling through Buenos Aires. And by "searched thoroughly," I mean every zipper for every pocket and every flap to every box (even a box of tampons!) was opened and rifled through. There are numerous cases of items "gone missing" from luggage that came through this airport. Usually, it's something small, which is easier for an airport employee to hide on his/her person. You most likely won't lose your favorite sweater, but you are likely to lose belts, jewelry, electronics, money, sunglasses, or even make-up.
Another tip: when boarding the plane, the flight attendants like to tell you that there is no room for your carry-on bag and you will have to check it (they can take it down to the plane's luggage bay for no additional charge). REFUSE THIS. Explain you need the items in your carry-on at all times and do not let the bag out of your sight. A smaller carry-on bag is an even bigger target for luggage theft, since it's easier to handle and it's obvious that a smaller bag would mean that more items of high importance are going to be easily accessible when the bag is opened. Do not let the flight attendants take your bag away!
Finally, if it's of extreme importance (i.e. your Great-Grandmother's engagement ring), leave it at home. I also always back my computer up onto an external hard-drive before leaving home, so I won't lose all of my files, pictures and memories if something happens to my computer.