The gap between the 404 and 400 is tough to "crack" as its full of urbanized areas and natural heritage.
An ideal bypass would look like this to me - red already planned corridors, orange new corridors:
This would grab traffic from London, Sarnia, and Windsor, provide a direct connection to / through Kitchener, minimize new corridors needed. You would probably have to tunnel a bit between the 404 and 400 though, that's not an easy corridor.