Ken,
I seem to have men picked off base frequently. I sometimes have men picked off 1B when there are runners on 1st and 2nd. What is the guy on 1st thinking? Several years ago after having something like 8 guys picked off in a 5 game series I mentioned this to the commish. I told him I had the baserunning settings on the most conservative setting. Mike told me that the settings had NOTHING to do with pickoffs, only baserunning when the ball is put in play.

I do agree with Fred, it seems to be random. Guys get picked off in PB in situations that in MLB they would be hugging the base.