Well you don’t state what application you are using to do the animations as in most cases how easy it is to do the task in hand is based more on the set up in a given app as the animation part is no different as to the needs of one character as it is for two, three or even four. In the case of animation tools my weapon of choice is Motionbuilder as once you characterize an actor the hierarchy construct for one character is the same as all the others so is easy enough to target the output to the desired platform, in this case Unreal 4.
Granted Motionbuilder comes with a price tag above an beyond what is available for free but trying to do complex animations in a application like Blender, lets toss Max and Maya into the mix, producing a usable result is like trying to write a book using a spreadsheet.
So to get back on point sure there are requirements and different ways as to an approach of having 2 characters interacting and consideration must first begin with the purpose that needs to be served
By the way if you deconstruct the “Matinee” example you should have a good base as to requirements