Switch on the combat accessibility options (slow motion on a toggle, enemies that don't flank, lower enemy accuracy, invisible while prone): they block no trophy. Only the Grounded Daily Run trophy cares about difficulty, so play everything else on Very Light. The run autosaves to a single slot: leave the game only from the hideout between encounters, because quitting during an encounter counts as a death. The game doesn't show which characters have won a run or which mods are done, so keep your own list.