Every once in a while there's a site that will refuse to work with uMatrix enabled, even if I manually allow everything and disable spoofing.

I've noticed this too. Every time, it was solved by disabling uBlock.

I use umatrix all the time and there are multiple sites where it doesn't work. I think part of the problem is that not all requests are actually shown in the drop-down for you to enable them. Maybe a popup or frame causes umatrix to miss it etc. For a blocker where the default mode is "block everything", it makes sense that this failure mode would be the dominant..

Have you used the built-in logger to confirm that it's actually uMatrix and not another extension? I typically have this issue and then find that the fault was with a uBlock filter.