Is it realistic that a one-time Guest mode user will go through the trouble of setting up font-size or other settings, before going to the website they intent to go?

Sounds like a poor experience to begin with. Perhaps it would be better to launch the Guest mode window, with the same Font size as the hosting profile, at the moment it is launched.

Regarding language settings: In Desktop (meaning non-CrOS), they only control which languages does Chrome skip offering translations, but it does not change the UI of the browser itself, which is dictated by the OS anyway. Is this valuable for Guest mode? Same question for Spellcheck settings (setting that up every time a Guest window is launched seems a time waste).

Re: one-time Guest mode user will go through the trouble of setting up font-size or other settings. I imagine they would if they have accessibility needs (e.g. can't see small text) - otherwise they won't be able to use the browser. 

Regarding language settings: That's not quite true that they don't control UI language: On Windows, they do.

Moreover, across platforms, language settings allow a user to undo an accidental "never translate", to enable or disable translations, and to set accept languages.

You are right that on Windows the language of the browser can be changed, but that requires a browser relaunch. Not sure how that would work with Guest mode, since nothing in Guest mode is persisted across restarts, where would the information be stored, without affecting other profile's language?

Anyway, I am not opposed to exposing more meaningful settings to Guest Mode's settings, but we need to come up with an explicit list of settings that make sense, and ensure that there are no technical limitation of enabling them.