Identify the information networks you want to have access to (for me, it’s information about user experience design, product management, fatherhood, South Africa, non-profits, and music).
Go through your following list and see where the overlap is — if there is a lot of re-tweeting going on of the same people, follow the person who gets re-tweeted the most. This will reduce your Twitter stream but still get you the information you need (and faster than before).
Once you’ve reduced your following list, make your network as large as possible with the “weak ties” who will give you access to all the information you need. Again, look at who gets re-tweeted a lot, use Find2Follow to see if you are missing anyone in your network, etc.