Easily missable - the apple!
Cautionary Note for Act 3:
The page does mention that the Apple needs to be "picked up," but it should be reinforced that you need to actually add it to your inventory (it's very easy to miss).
Example:
In my playthrough, I referred to this page, and spoke to the Ox to trigger the quest. The Journal notification came on screen and audio events triggered. I then falsely assumed the Ox had transferred its apple-form to my inventory. This assumption was false: it's still on the ground in the shed.
When going into the lower city, you will NOT get a journal update notification that the quest failed (as of patch 4), although the quest will move to completed status.
It wasn't until far into the third act that I noticed I failed.