Hardened Detective difficulty:
Beat Private Investigator difficulty.
Mythos Master difficulty:
Beat the game under Hardened Detective difficulty.
Private Investigator bonuses:
Beat Private Investigator difficulty to unlock concept art, character renders, and background art renders.
Hardened Detective bonus:
Beat the Hardened Detective difficulty to unlock the Craig Mullins gallery
Getting an A rank:
To receive A rank, you must collect every journal entry (13 for Jack's Diary, 18 for General Evidence, and 6 for Mythos Tomes), find the rifle in the refinery, save Ruth from the rafters, and make sure enough sailors survive the boat assault. If that's not enough, you have to do it all in under three and a half hours, saving less than 30 times. Good luck!
Variety Store safe combination:
The combo on the variety store's safe is 2-6-1-2.
Thanks to Revolution Readers Billiam, filp, and MattC!