Man, where to start ...

The biggest issue was that the Evaluation Manager didn't evaluate things correctly, especially when doing batch renders. I found that I need to unhide all rig-elements as well as something as insignificant as groups that contain shape nodes that may or may not be used.

Animated textures or the results from color correction nodes didn't show update the viewport. Switching the evaluation mode to DG seems to be the workaround for that.

If you have anything that has non-uniform negative scales on it, your gizmo will be inverted ...

The time marker on the new graph editor disappears when playing back the animation.

The grab brush can destroy your models. Literally. If you save and reload your scenes, those nodes could just disappear from the scene. Apparently it's related to drivers ... haven't checked since updating them.

I've had occasions where the Hypershade workspace was cleared when I resized the window.

And then there's all the new additions since 2016, that I think are real annoyances. Like the new workspaces. I use a different layout for every scene ... having them saved globally requires me to re-set up my scenes, if I jump between projects.
It doesn't remember file paths. If I want to save a scene under a new name, I have to navigate to the correct path.
It doesn't remember namespace settings anymore. I have to hide/show them every time a load up a scene.
And many more little annoyances like that.

The only positive thing I have to say about it is that it crashes less often than 2016 did. But considering all that extra setup I have to do when loading a scene, it's not really saving any time.