In fairness, to Matt Parker and Trey Stone, a good portion of South Park's "charm" is that many of the voices aren't done by professionals but by themselves. Granted, they still used "professionals" for the key female parts like April Stewart, Eilza Schnider, Mona Marshall and the late Mary Kay Bergman. But even so, let's say hypothetically instead Matt and Trey doing many of the voices they had for instance:
Grey Griffin - Stan Marsh, Bebe Stevens, Bradley Biggle

Tara Strong - Kyle Broflovski, Scott Malkinson

Jennifer Hale - Eric Cartman, Kenny McKormick

Dee Bradley Baker - Butters Stotch, Timmy Burch, Gerald Broflovski

Nolan North - Clyde Donovan, PC Principal, Phillip, Stephen Stotch, Dr. Alphonse Mephesto

Steven Blum - Craig Tucker, Stuart McCormick, Ned Gerblanski

Jeff Bennett - Tweek Tweak, Randy Marsh, Officer Barbrady, Terrance, Dr. Gouache, Father Maxi

Jim Cummings - Mr. Garrison, Mr. Mackey, Jimbo Kern

Phil LaMaar - Token Black, Jimmy Vulmer

Sean Schemmell - Sergeant Harrison Yates

This is interesting and would change the show a lot. But in a good way. I'd love to see the same for Family Guy.