Earlier quoted context omitted.
Some of the sophistication is not really in the technical breaking of the game or protocol anymore, figuring out if something is plausible might yield detections that you cannot "cheat" because it no longer matters if your cursor clicked on a head at the right time or not, it matters if your posture/reputation/experience makes your behaviour plausible. Cheating and anti-cheat used to rely a lot on the pure technical…
It's hard to balance around those sorts of things. For example, imagine a cheat that gives the player additional info about where enemies are and their state (ie: health). Even if they are of totally normal skill level in terms of movement and aim, that info will allow them to be substantially better than others. How are you going to detect that, and differentiate it from players who simply have a great sense of map…
The only group you'd punish with that is skilled players that lose their account (and create a new one), but if you use a moving skill window they can grow back into their plausibility pretty quickly, and it's a small cost compared to everything else. And you could even mitigate that by making things like the first 10 matches require a different plausibility score than the matches after that.
And with different I don't mean "no scoring at all" or something like that. But a cheater tends to not cheat "a little bit". You might have togglers, but that sticks out like a sore thumb (people don't suddenly lose or gain skill like that). And even if that fails (lots of "cheating a little bit" for example), you've still managed to boot out the obvious persistent cheating.
And that's just with 1 example and 1 scenario. Granted, that bypasses the fact that it is still difficult and doing it broader than one example/scenario is even more difficult, but that's why I ended the previous comment pointing out the difficulty and associated cost, which goes hand in hand with the balancing difficulty you pointed out. Even tribunal-assisted methods (not sure if Riot games still does that) have the same problem.