Well... everyone is different. Blah blah blah.
If you find a set that respects the ratings, then the game isn't that much of a challenge [at least against the computer] and if you want a challenge, which is secretly what most players want, then you are going to end up with a slider set that is crazy hard just for the sake of being hard. For example, I have seen people tell you to use like 5 QB accuracy, and in doing so, I have used Tom Brady/Pyton Manning/Drew Brees/etc and had a hard time throwing a Curl or an out route with any consistency. When using a super Star QB is a chore, it isn't fun. It is just hard for the sake of being hard. Yet, if you increase it all that much more, then I find myself going 16/20 and 3 TDs with Tim Tebow or Colt McCoy. I am just not sure there is much of a happy medium.
This is increased exponentially with different individual skill levels and preferences. I just try to find a set that does gets as close as I can at respecting individual ratings and match ups when the AI plays against itself [the user can only control one palyer at a time, so the other 10 are just playing out their ratings/assignments.] For example, I like to control the Jack linebacker in the 3-4 or sometimes a safety in a Seam/Curl-Flat assignment and let my AI pass rusher do their job. Other times I want to control the RE, who always has a much harder time against the LT than the LE has against the RT, and try to even the odds with some user pass rushing... but that means I need my linebackers to do their jobs, and I don't think EA has even programmed these players to really do their jobs right in the first place no matter what the slider settings or ratings are.