I've played over 30 seasons in manager mode using OOTP6. I don't remember what difficulty I selected, I know it wasn't the hardest or easiest though.
I spent my first two seasons finishing in dead last place, and improving to a .400 winning percentage and still finishing last. My owner didn't want me to come back, at which point I looked at the offers I had in the offseason, and signed with a team that made the playoffs in season 1, and finished 3rd in season 2. Since that time, I've won the World Series more than 50% of the time I've been in the playoffs. I've been in the playoffs probably 70% of the time. On seasons I have missed the playoffs, it was USUALLY attributed to key injuries to star players (starting pitchers usually) or a rebuilding year after too many players retired or got traded due to severe talent drops. My minors consistently run amongst the best simply because I scout prospects to trade for when I am looking to move some of my veterans before they sign contract extentions. I'm getting ready to start a new league with the difficulty set on hard, just to see how hard it is.
From my findings, it is easier to win if you PLAY the games. If you strictly sim the games, it doesn't seem to make a difference in manager mode vs. non-manager mode. It pretty much is dependant on how well you scout talent, how you use your pitching staff, how you use your depth chart and lineups, how often you look at your team to evaluate weeknesses, and how good you are at retaining star players while they are stars and getting rid of them before they flop.
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-Chris
TWIB - Commish - Cleveland (1884 - present)
MCBL - Commish - 50, 55, 59, 65, & 68 World Champion New York Yankees
NTBL - Commish - Chicago Cubs (1918 - present)