I've been on Twitter since January 2008, follow 114 people, have sent out 924 tweets, and have 10 "followers" who probably never follow a word of my tweets. Most of the people I know in real life don't use Twitter, and I discourage followers from the Twitterverse by not following them back. A few months ago I even blocked most of those I'd picked up.
Twitter works well for me as a source of news and casual editorial comment about the issues that matter to me. It provides an interesting stream that supplements Google Reader with sources that I would otherwise miss. When I discover interesting new tweeps, I follow them too; on Twitter or on Reader if they have a blog or publication. Most of those whom I follow have thousands more followers than the number they follow themselves.
But for me it's hard enough to keep up with just 114. I try to skim through every tweet, but occasionally resort to filters like My6sense or TwitterTimes.