Everyone has their own preferred way of doing things...and that way may vary depending on where one tours and for how long.
For my longer tours and self-supported expeditionary tours where I must carry a lot of spare food and water (up to 26.5l for my desert tours), I go with 4 panniers, a handlebar bag and a roll across my rear rack (plus a rack-top load under it).
For lighter touring, I use either only a Carradice Camper Longflap or that and an Ortlieb Large handlebar bag, as shown here:
http://thorncyclesforum.co.uk/index.php?topic=11787.msg85858#msg85858 This package is small and light enough for me to simoly remove and carry whenever I leave the bike.
In-between, I use various combinations of the above (I have two complete sets of Ortlieb front and real panniers and handlebars bags, so I can tour with four front panniers...or four rear ones but usually two front and two rear). I also have some rack-top bags I can use at the rear if I wish.
As for theft avoidance, I
always place my valuables (money and electronics, camera, travel documents) in my handlebar bag and I
always take it with me when I leave the bike for any reason. I equipped my Ortlieb panniers with their anti-theft tethers (fine stainless steel cables) that I secure with my frame-mounted ring-lock's plug-in cable or chain (depending in where I am touring). They wouldn't deter a determined thief but they would slow someone and deter a snatch-and go kind of theft. I also have my more heavily loaded rear pannier mounting rails equipped with a second set of mounting hooks. This also slows removal, a boon to avoiding theft. My underseat saddle tool bag is secured with the same cable that secures my saddle and also latches into the bolt of my frame mounted ring-lock.
I leave the bike unattended and in the open as little as possible and of course make sure it is locked securely. If one is staying in a hotel, the concierge will generally be happy to store it in a secure location for you.
I also have my bikes equipped with remotely-controlled motion-detector alarms secured under the saddles. They noise they make is pretty noticeable (113dbA) and us intended more to startle a thief who might not expect it and to notify me, 'cos most people in cities seem to ignore alarms of any kind. I've found it really useful for my forest camps to deter porcupines and other small animals who might otherwise gnaw into my bags. It works great with the remote control for startling/deterring bears and mountain lions.
In all my international travels, I've never lost anything due to theft or pilferage, unlike here in the US, where I have lost some small items to pilferage, generally by people who acted on impulse and were looking for a souvenir.
I still remember a small village outside Nikopol in Bulgaria where I stopped for supplies. An older gentleman greeted me as I was in the process of locking my bike and urged me to refrain, saying his was an honest village and they would take it as an insult if I didn't trust them enough to leave it unlocked. After some thought, I left it with him -- but still glanced out the store window. He stayed next to the bike for all the time I was shopping and it came to no harm. Another time in Turnu Măgurele Romania, I needed to leave the bike to use the toilets located
under the city park. While I used care to lock my bike and take my handlebar bag, a gentleman there also volunteered to watch the bike and did so honorably and carefully. We had a nice chat lasting about 30 minutes afterward and he told me of his time spent in New York City "where you couldn't trust people like here".
With care, I think you can have a good experience in many places while touring. Unfortunately, I live in an area of extremely high bike theft and a number of tourists' bikes and all their gear gave been stolen as they stopped for groceries on their way through town. Most were crowd-funded replacement bikes and were able to continue their tours, but not in the same way as they arrived.
Best,
Dan.