I agree with you, chaos is really fun ^^ Don't you think that the game would be even more interesting if it was activated by default ? That way each run would feel more unique.
Adding negative effects regularly seems like an excellent idea to keep the game challenging and interesting ! (Maybe after an active duration instead of levels to avoid penalizing people with the "careful study" skill and encourage players to be more aggressive ?)
One thing that I would really enjoy too is a clearer presentation for cumulative skills : for example instead of having "vampire touch" every time, have "vampire touch 2" when you pick it a second time, etc... that way it would be easier to track down if a skill is relevant or not on long runs. Also, it could also be easier to see on the left column if you present skills in a similar way instead of a never-ending list that continues off-screen. Of course the ideal way would be to get a new icon for each color when there is chaos, but you could have a line for poison skills for example, with a list : green poison 3, blue poison 1, orange poison 2, etc...
When leveling up, having this kind of presentation and screen cards that don't overlap the column on the left could bring a more tactical feel, because you could clearly see what you already have and pick new skills accordingly (it is especially useful on very long runs where you kind of lose track of what you got)
Putting a limit to offensive skills so that they can't appear again when they can already one shot every enemy could be cool too, because there is no need to have green poison 20 if no enemy has more than 10 HP for example. Same thing for healing skills and health upgrades if you put a limit on the max HP players can have.