It can be done, but in my opinion it would only work with a small dedicated group who's schedules meshed well together. One of my co-workers and I had a two person league together in that we started with THQ UFC 2010 and it was a blast.
We started with a draft where we each selected four fighters per weight class. We would use the entire roster, but we "owned" our drafted fighters and would only let the other guy control them if it came down to a championship or #1 contenders type match. We would use the rest of the fighters and if you had a win with a fighter, you had the option to continue controlling that fighter in their next fight. Although, this wouldn't always be the case if it made sense for them to fight one of your drafted fighters.
The roster was fairly deep, especially since it was easy to share CAF's in the THQ games. When we started we based everything off of real life and ran with it from there. We kept up with records, belts, rankings, win/loss steaks, awards like Fight of the Night/Year, Knockout of the Night/Year, etc. We had PPV's, Fight Nights and once a year we even had a Pride card. Then at the end of each calendar year we had the option of swapping one of our drafted fighters, but we could only change if we had a current winning streak with that fighter at the end of the year.
At the time the company that we worked for was small, so my co-worker and I shared an office. We would spend a decent amount of time at work creating cards and figuring out what would be the next best match-up for each fighter, etc. It really was awesome to see how each fighter fared as the league progressed and who would rise up or fall off.
Unfortunately, my co-worker went and had two kids since then and he's never upgraded to XB1 or PS4 so now I have to fill my UFC league void my playing against the CPU. Which I had an okay time against the CPU with UFC 1 and if the AI improves I'm sure I can more than made due with UFC 2. I'd love to see a online mode like that one day because I'm sure it would push online to another level.