Hi,
I am running into the exact same problem on the same Mac model (MacBook Air M2, macOS Sonoma 14.2.1). The game ran fine for months on this machine (I bought it last June). I am running the latest version of Cities Skylines (1.17.1-f4).
Since two weeks, when I start the game, mouse clicks are unresponsive on the game interface, either on the main menu or in my city (when I choose Resume game from Paradox Launcher). It does not appear to be an offset issue as interface or menu buttons highlight when I hover the cursor over them, but clicking does not produce any effect (not even the click sound heard ingame). In several occasions (I was not able to reproduce them), game interface worked by double-clicking on the interface elements (tools, roads...). The game is not frozen, sound and ingame music play normally.
I previously ran into this mouse click issue once last summer, and was able to solve the issue by disabling V-Sync in the Options panel of the game.
No luck this time: I tried every tip related to this issue I could find: activating an item in Steam workshop, remove all mods, disable Steam overlay...
I removed the game, including all saves, mods, preference files I could find on my computer, rebooted, reinstalled it (without mods), same thing. I am stuck either on the License Terms agreement confirmation box when I start the game from 'Play' button on the launcher, or cannot do anything in my city except moving the camera while moving the mouse towards the screen corners when I start the game from 'Resume' button.
Obviously, same behaviour while using an external mouse or the trackpad. Both work perfectly in other games or applications.
My game is now unplayable.
Any help would be much appreciated! Thank you.