Is it ethical to submit to a journal if I know the editor-in-chief? Is it ethical to submit to a journal if I know the editor-in-chief?
I'm curious about 3 different cases:

Case 1: We know each other (from talks and emails) but never worked
together.
Case 2: We haven't worked together, but are currently in contact
about a potential collaboration.
Case 3: If I am one of the editor-in-chief's collaborators (but the
paper submitted is not part of the collaboration).

In all cases, I don't know if the editor-in-chief is going to give me an easy time (I am not even looking for that) or a hard time. I mean no promises. I will even ask, in the cover letter, for my paper to be reviewed by at least two referees to comply with my University's regulations (so that I can use it for promotion purposes at my Uni).
There are no ethical concerns about submitting. If there are any ethical concerns, they are completely on the other side. The editor should make some arrangements so that people are treated fairly in the interest of good scholarship. The normal way would be for them to pass all decisions about your paper to someone else.
Editors know a lot of people. Being named an editor shouldn't close out opportunities for those you know and have worked with. But care should be taken so that the process is fair and transparent.
Stepping aside also avoids the possibility that you will blame your &quot;friend&quot; if the paper isn't accepted.