Being a relentless consumer of stats, I've grown to love the Commissioner mode for quite a few reasons.
Also, it's nice to get a sample of all the different mind-sets people can have when running OOTP.
So, as far as me, I like to start out running my team, the Cubs, with the closest-to-current MLB rosters. I'll guide them for, say, 15-25 years, or until I've won a bunch of championships.
Then, as all of the players I now follow in fantasy baseball grow old and retire, their names begin to litter the list of career leaders.
This probably is the best part. Say you pick one of the worst, small-market, in-debt teams, with a useless farm system, a huge payroll and a ton of old guys. You trade what you can for prospects, and then enjoy two to four years of top-five draft picks. At the same time, let all the bad contracts expire without signing any big free agents. It's rock bottom.
It's also a challenge that can take anywhere from roughly 10 to 20 years to produce a championship.

But it's loads of fun -- especially acquiring and following prospects.
In my latest instance, I did this rebuilding thing with three more crappy teams, and cracked the 100-year barrier. It's an OOTP5 league (I know, I know -- by the time I discovered OOTP6, OOTPBM was already being promoted).
Ultimately, it's quite entertaining after 100 seasons to browse the career leaders and hall of fame. And, as you all know, it takes a damn long time to go through 100 seasons running at least one team. I've had this particular file going for close to two years, I think.
Lastly, as I ramble on unabashedly, I'm downloading the free version of OOTP5. The story is, I got it the first time a few years ago. Then my old computer finally broke down, so I got a new computer (couldn't transfer OOTP5 because of the license) and downloaded the free version with the free-agent bug.
But now, with MAJOR THANKS to Markus, Marc, and whoever else had the gumption to re-patch a three-year-old game, I'm downloading it again.
I'm also proud to admit I've come to terms and am comfortable with still-unidentified (not going to say it).
Spring is long, especially in northern Illinois, and it just started. This just means I'll have to start a new league on my freshly de-bugged OOTP5.