Having used Twisted for a few projects and now using Pyramid for another, I'd say there are two big problems with Twisted that kill the experience for new developers:
1) The documentation is terrible.
Even though there's a lot of it, and even though the API documentation is pretty good, the 'narrative' and tutorial-like documentation is downright horrible. It tries to cram so many things into the same contrived examples at once, that reading it creates more confusion than giving insights. Take for example the 'evolution of a finger client', which is one of the first things you get directed to when you want to start 'learning twisted'. Instead of introducing some basic concepts that affect design decisions and then working them out in simple, individual, small examples, it starts out with a server example so trivial that it's completely un-representative of how a typical Twisted service would look like, and then, in a few pages, crams so many things into it at once that you have to go back, re-read and actually try to implement and run the example yourself to figure out what (and especially: why) the heck things are working like they are working. In one swell swoop it 'teaches' you Twisted by throwing around component-based programming, Zope interfaces, adapter classes, the factory pattern and how you can basically use it everywhere even though there's no real reason to do so, how you can expose 4 different protocols talking to the same service at once, how you can add asynchronous versions of the same services, and so on. All of it combined in a single 'Twisted application' that reads like some kind of intentially obfuscated crypto-program that somehow magically does all these things.
Compare to that the Pyramid documentation, which is absolutely fantastic and got me up to speed and writing very clean and stable applications in just a few hours. Where reading the Twisted docs the main thing going around in my head was 'wtf do I have to do here and why', while with Pyramid it everything immediately made sense. Note that I'm not saying this is a problem with Twisted itself, just with the way the documentation tries to explain how to use it.
2) Twisted doesn't advertise its specific benefits and downsides very well.
Superficially looking, many people might think Twisted is just like other web-application frameworks like Pyramid, Flask or Django, but it isn't. You can do most of everything using Twisted, but it's much lower-level than those. Just like this article mentions, Twisted is more like a toolbox to create event-based applications than it is like a web-app framework. This makes it a lot more flexible, but also more complex. While this allows all kinds of use cases that nobody would ever consider e.g. something like Flask or Django for (e.g. game servers, chat servers, etc), it also means that if your application is 'yet another web application', the other options are probably going to be a lot simpler and cleaner than using Twisted.
I think because Twisted doesn't want to choose and declare what it's main strengths and purposes are, it's attracting many developers of applications that are a much better fit for the more specialized web-app frameworks, leaving them with a really bad experience, spending too much time figuring out the framework and ending up with cryptic gibberish that doesn't really implement any actual application logic.
Don't misinterpret this as a critique of Twisted itself, I still like it a lot, exactly because it is so flexible and generic. It's just not the best tool for most web applications, but if if you are implementing some kind of event-based application that doesn't fit the philosophy of the other popular frameworks, it's extremely powerful and well-designed. I think the Twisted community should make this difference more explicit for new developers.