First off, I am no master NCAA player at all, but have been playing for years. I'd probably get killed online!
All I play is against the CPU, on All-American, minimal slider tweaks. Anyway, I call my defense according to the formation of the offense. If they come out in a strong run set, I'll go 5-2 or 4-3. if they are running and running and running real effectively I'll even go Goaline formation for a few plays, mixing man and zone coverages till they stop.
Same applies to passing. if they come out in a 3 WR set I almost always go Nickel, but it's important to occasionally throw in Dime or something like 4-3 over/under to mix it up.
If the cpu is obliterating me in passing I switch exclusively to a Quarters defense, and unless the yardage they need for a 1st down is huge, I play press coverage with the Quarters, if the QB is mobile I always pinch my line inside to prevent a QB draw.
I don't blitz real often, especially from the CB position, but I do mix up random OLB blitzes and inside blitzes. I seem to *almost* always have great luck eventually slowing them down and keeping them from many points, but sometimes it takes just weathering their storm and sticking to the defensive game plan. if my "Quarters scheme" to slow the passing is cheesy, then I guess oops! But hey I guess the object is to win lol...