What is the load calculations? You may not even need a 320 amp base.
That said, in most cases a 320 amp base will accommodate two load side conductors much easier than a 200 amp base will.
Whether or not you can have two different sized conductors will depend on the lugs. Some bases have lugs installed, some just have studs and you provide your own lugs depending on your needs. A single lug designed for two conductors, will usually require both conductors be the same size. A multi port lug will allow for different size conductor (within listing range) in each port.