Everyone has their favorite chests runs that they do and their are good arguments for why their favorites are their favorites such as chests per minute, rare drops, etc.
For a long time my favorite run has been the Maatu Keep run:
I've used so many lockpicks doing this run that I decided to see what my profits vs. losses actually are, of course you expect to have much higher losses when using lockpicks at 1,250g each, but there is a possibility for those hidden gems dropping in this particular run also in hard mode elite tomes help pay for some of those expensive lockpicks.
For this study I used 80 lockpicks as that is the standard amount for 100k buying from players in kamadan which is the cheapest way to get them without having a guild which owns a town.