Well, I think E-40 has the edge over C-Bo because of his constant invention (and re-invention) of Bay Area Rap phrases and whatnot ("Ya smell me?" "Fa Sheezy!", "Mustard and Mayonaise", and too many others to name). Bo was instrumental in establishing the "dark" sound of Sac-town rap, but he's basically kept it lyrically gangsta (nothing wrong with that, just saying Bo's a little more limited in his approach, dope as he is).
Also, 40's not afraid to work with different rappers outside the Bay Area (i.e. Baby, Juvenile, Ice Cube, Mystikal, etc.) Granted, not every collab he's done has worked, but you gotta give 40 Fonzarelli credit for experimenting. PEACE!