There is no simple answer...
Here are your generic options with their pro's and cons. Others will most certainly comment on my opinions
1) Basic Luggage lock
Pro: Comes with your suitcase.
Con: Normally easy to pick/break. Can't fly to US with them.
2) Quality padlock.
Pro: Secure for most flights. Hard but not impossible to pick. Some strengthening of lock so harder to snap.
Con: Can't fly to the US with them.
3) Cable Tie.
Pro: Easy to apply. Easy to remove (if you remember to pack pliers!)
Con: Cable ties all look alike. You wouldn't know if someone swapped one on you. Easy for someone to remove.
4) TSA locks.
Pro: Relatively secure. Only TSA should have the keys to unlock them (cough!). If unlocked via TSA key then lock will show a "red flag".
Con: They look similar to each other.
5) No locks.
Pro: Easy for you.
Con: Hmmm. I'm not going to go there!
6) Secure Luggage cable ties.
Pro: Easy to apply. Unique numbers show tampering.
Con: Easy for someone to remove. (You would notice though).
7) Luggage wrap.
Pro: Easy. Easily tell if tampered with.
Cons: Cost $, Easy to remove.
8 ) Baggage mesh.
Pro: Good security. Similar to padlocks but covers all pockets without multiple locks.
Cons: Won't work for US trips unless using TSA locks etc.
I think it all comes down to a level of security you want to have. If you travel to certain countries and someone manages to slip something in your bag... basically you're stuffed regardless if you locked your bag or did anything else to it to help secure it. Try proving just how well you secured your bag, even though when it arrived it had no locking mechanism...
If you travel to the US, you need to either unlock your bags, use a TSA lock or cable ties. If something can't be easily snapped then boltcutters/pliers are a quick method to remove it.
As for me. I prefer trusty padlocks that I have the keys to. Sure they can be picked, but hopefully my baggage isn't sitting there long enough for someone to want to....
I'll soon be moving towards TSA locks for my bags. Still looking for somewhere that sells a "keyed" version (don't like 3 number Combo locks for baggage - but 4 is a lot better) and/or I can get a 3 pack for ~$20-$30.
I am also slightly leaning towards using the numbered cable ties.