I feel like there's some incredible magical thinking about organised crime in these pieces, where people believe that it's this unstoppable elemental force or like trying to catch the wind or something.
History shows that to be completely false.
Organised crime absolutely can be stopped and absolutely can be a good enemy and absolutely does have a reason to stand and fight in many cases. Outside of comic books, organised crime organisations are not regenerating hydras, and decapitating them or just killing or jailing most of them can be very effective.
The problem then isn't regeneration but the vacuum, both in power and black market economy, that exists. But that can lead to more adventures.
As for the idea that killing organised criminals will have consequences in the society they are part of, absolutely! But so should cultists. And this is something D&D tends to gloss over. The Baron's family will be mad if you kill him for being a criminal, but guess what, they'll be mad if you kill him for being a cultist. If one would get your throat slit by an assassin, both would. The problem is a different kind of magical thinking re cultists, where there's an assumption that killing them never has consequences.
I'm not saying cultists aren't awesome, but the OP is flatly right that they're overused and used lazily, particularly by official adventures through all editions.
Mercenary companies of a nasty bent are often good enemies. They have access to magic, lots of combatants, may have exotic creatures, golems, etc and tend to be possible to destroy.
Magic or martial arts schools are a possibility, though you do probably want to make them adult educational institutions, as it were.
Aggressive mercantile organisations can work. I have an East India Company but worse type organisation in my game which frequently clashes with the PCs. They also have a lot of spies and catspaws and so on.
Unpopular rulers, especially oppressive ones, can work really well. As can their agents in other societies.
Non-cult but dangerous religions can work. In my setting there is an entirely above ground and open non-evil religious group which seeks dominance and is willing to war to get it which also clashes with the PCs plenty. No skulking cultists they - indeed they may sometimes be on the same side as the PCs vs cultists.