Not difficult but it is a process and the more of a perfectionist you are the more knowledge and tools you will need.
Depends greatly on the subwoofer (RELs are by far the easiest because of their passive radiator) and the speakers (speakers with lower output are harder to integrate unless you plan to high pass, which I will not do.
Two subs are more difficult, especially if you don't know the proper method, but the results are better.
I would not integrate a subwoofer without a using some form of measurement tool- e.g. a microphone, RTA software and full bandwidth pink noise tracks.