Over penetration can be, but shouldn't be, a problem. Missing is a far greater problem, and placement is the first consideration if you have to shoot a human aggressor. (Or an animal.) Adequate penetration is not an option, and if you look at the detailed study of the FBI's 1986 shooting in (suburban) Miami, under penetration was an issue. Their experience was an impetus for the ballistic studies done by Fackler, at al (IWBA) and continued by Dr. Roberts. Among other lessons: if you expect a problem and can't be elsewhere, pistols are not the answer. Long guns are.
The penetration standard in calibrated ballistic gel is not a direct correlation of the amount of penetration needed on a human - it is a means of having a consistent measure, just like running times in fitness tests are an expedient manner of testing oxygen uptake. If you have to shoot from the side, the round must penetrate the arm complex to enter and penetrate the vitals (high center mass).
Me? I usually carry an auto-pistol, and I chose them based on my performance. If I carry a revolver, my usual preference is a medium velocity lead SWC, such as a standard .38 in my M66. I can and have qualified with full power magnum loads, but objectively, the odds of good placement and rapid repeat shots are far better with the .38s.
I have on many occasions cited to the Patrick and Hall text (3rd edition). The ballistic lessons provided are not directly applicable outside LE, but they are a closer fit than most misinformation. Perfect penetration is when the bullet stops and falls in the clothing on the far side just after exiting the chest. It's a rarity, or a fantasy, and not what I consider. One needs to know the proper targeting on a human aggressor and place rounds there consistently.