major sites of protonation and deprotonation

To find the most likely places for protonation/deprotonation, you need to see where adding/removing a proton will create the most stable conjugate acid/base. So look for things like strong inductive effects, possibilities for conjugation, etc. Just remember that sometimes the easiest place to protonate is not productive, so you might need to look at the second or third best site before you find where to go with a reaction.

do you look at a resonance structure or just the molecule itself

Looking at resonance structures will help you, yes.

I dont know how you collectively put together resonance, inductive effects, hybridisation and electronegativity in determining the most acidic proton, surely some of these effects will end up giving different acidic protons?