I have been, and am in, a lot of sim leagues. We use Baseball Mogul 2007. It's fun...
Of course, with my attachment to all the Nationals players, it is hard to make the team really good. It took all my gut to trade Nick Johnson the other day.
My advice: keep Zimm, Patterson, Cordero for sure. Trade the rest. Make a good, young core.
Edit: Keep Nick if you want to too. But, if you get a good offer, trade him and all others besides the ones I mentioned above.