I have comeback to the 4-3 I used to play a lot of 4-2-5 and multi D. I find that when you use the 4-3 Normal no blitzing with the MLB spy and using the MLB as your player you can stop the run. Now that doesn't account for when they go 4 wide. But I stay in the 4-3 against anything smaller than 4 wides. Then you can get into the Nickel if you feel comfortable using a LB or S in coverage. If not go to the Dime the key is using one of the LB's most of the time I like to make sure it's just a spy so he has no real coverage responsibilities on the play. I will then be able to attack a run play attack the QB if he is on a run play drop back into a zone or cover a TE or RB if they come into the middle of the field. Or attack the QB if no RB/TE come into the middle of the field. I always like to try to keep my S's over the top if i'm thinking the user will be passing. Don't be afraid to use your CB's as soon at a deep ball is thrown since you don't really get called for PI much you can get a little physical with the WR making it easier for your player to make a good play on the ball. If your CB is beat or in a trail spot you will always have that S back there to take control of to make a big hit or make the INT. Or worse case make the tackle.
Recruiting well will also help I don't recruit a DE unless he is 4.4 or lower speed. Now they normally won't have great weight to them but they don't get beat outside and attack the QB well when your not using them. If your in a long 3rd down and 15 against a user I will go to one of my DT or LE DE. If you can get the push with your DT on the play most likely one of your very fast DE's will be in on the QB to either get the sack or force him into the DT's.
Example: Alabama OD 2nd Year
DE- two Freshman
Curtis Dargan 6'2 193 lbs 85 SPD 83 AGI 84 ACC
Doug Murphy 6'2 223 lbs 86 SPD 82 AGI 88 ACC
As you can see these two guys are light but ultra fast. You pair them with 3 DT from 382, 303, 306 and 283 lbs and you got great stuffers in the middle and quickness on the outside.
LB- Soph, Junior, Soph, Fr, Soph
OLB- Jerrell Harris 6'2 227 lbs 88 SPD 86 AGI 88 ACC
MLB- Ronaldo Mcclain 6'4 257 lbs 86 SPD 80 AGI 82 ACC
OLB- Donta Hightower 6'4 253 lbs 84 SPD 83 AGI 84 ACC
OLB- Todd Abdullah 6'3 231 lbs 84 SPD 84 AGI 83 ACC
MLB- Courtney Upshaw 6'3 233 lbs 85 SPD 84 AGI 85 ACC
Now as you can see from the DL to LB's your not going to get out quicked often if you have 7 in the box controling the MLB with S's over the top you can stop a lot of people.
Now look into the future with the recruiting class I have going week 13 season 2.
DE- TJ Mcintosh 6'2 235 lbs B PUR B- SPD B ACC
DE- Bob Bracey 6'4 199 lbs B PUR B+ SPD B ACC
OLB- Drew Moore 6'2 220 lbs B SPD B- AGI B+ ACC
Now for my sleeper kid those 3 above are 5 stars but this 4 star kid looks like a beast.
OLB- Aaron Wiggins 6'0 234 lbs B- BSH B PUR B+ PRC B- SPD B AGI B ACC
I got in late on Wiggins and trail 3 Pac 10 schools but it looks like it might go into the offseason with him and if it does I got a great shot at him. Now in ending you can form any defense to your liking with great recruiting. There is a defense for everyone on this game you just have to find it and recruit it.