From personal experience, I have found Unique Items by "Investigating" a region, from killing Alpha's/Champions, and I even found one once just by traveling from one region to another. That was quite the surprise haha.
I am trying to remember if I have ever found anything by gathering, but I can't remember for sure, so I can't put the Gildre stamp of approval on that...
And of course, making a new item. I haven't done that one personally. I never have the right items...