I think sportsfan30 had the right idea with adjusting difficulty for games like this. The things making it too easy are that you have infinite money, tons of helpful item drops, and most fights are easily avoidable. Tuning difficulty to make individual fights harder to win is a worse way to do it than making attrition more noticeable and unavoidable. It undermines the premise otherwise: strong heroine degraded by weaklings. Reducing the supply of items and money/carry limits on purchasables, making dropped/found items come with drawbacks or have a more limited scope of effects (can only find HP potions that are tainted, no repair kits, neutralisers, or purification items), and increasing the chase speed of ambushing enemies so you can't just avoid them all contribute more to both the theme and making gameplay challenging. That's my plan at least for once the translation is done to create a difficulty mod.
I know when I'm trying to do a scuffed run, that's usually more impactful than any stat debuffs I give her. No healing items allowed, use Repair Kits only when clothes are completely destroyed, not purging Aphrodisiac unless it is at max, deliberately letting ambushes actually connect, etc.
One thing I think would be interesting to try would also be adding more unavoidable fights where you start at a disadvantage. For example, the Matango fight at the bottom of the swamp can usually be cleared out in a single Bladestorm, making it a non-issue, despite it being a nest you have fallen into. Starting ambushed, having additional hit chance penalties, additional waves of enemies, etc. would make the encounter far more interesting. That might be a little bit more challenging to add to the files, but it's something I'm thinking about as well. Same idea, but making more chokepoints where you have to fight an ambush.