I don't count Sam. For me, the main characters are the ones that mad it into the movies as part of the main focus and the ones that became muppet babies. I see Sam as secondary. There are many episodes of TMS that IO've seen where Sam isn't even seen.
According to the guy that does Homer, he just switches most of the time as do the others on the Simpsons. Of course when two characters voiced by the same guy talk at the same time, there has to be some mixing of pre-recorded stuff. Not sure if this is the same for other voice actors though.
It's amazing how some characters done by the same person can be so different in voice and personality. When I learned that Rizzo and Kermit were done by the same person, I was amazed. Same with Pepe, bobo, and Jonny, 3 very different characters (except the laugh). And the difference between Elmo and Clifford is HUGE! And Frank's 3 main characters on TMS and Sesame all sound totally different to me.