I cannot speak to all the various use-cases that people have brought up, but it seems like a fair-number of people looking for this would be satisfied if multi-branch pipelines just supported an 'exclude regions' flag. You get that behavior with regular-pipeline, but not multi-branch pipeline.
In my situation (and seems like others have this as well), I have directoryA/Jenkinsfile and directoryB/Jenkinsfile, and I wish to trigger pipelineA when commits are made to DirectoryA, and pipelineB for DirectoryB. There are [a few solutions floating around|https://stackoverflow.com/questions/49448029/multiple-jenkinsfile-in-one-repository/60316968] that effectively have both pipelineA and pipelineB starting, doing a 'validate' step, and then pipeline logic to short-circuit, causing completing when the commit is on the other side. But I'd really prefer that the build NEVER start in the first place for the wrong pipeline. Commit to DirectoryA -> only PipelineA is triggered. That amounts to PipelineA configuring "DirectoryB" as an excludes region (and vice versa).
That said, there are a bunch of use-cases all entwined herein, and this is only one of them. But... it seems like a fairly well-defined one that might mitigate a lot of people's issues.