OK, I wish that I was about to give you some really cool technology that you can use to follow hundreds or thousands of twitter folk. But I'm not. This is so ridiculously simple that I almost feel silly telling you this, but here goes:
Set up two twitter accounts.
That's it. You set up one account where you follow everybody and their brother. You set up another where you just follow your closest friends and relations. If you're online, you could have one account open in, say, Firefox, and another open in Safari. With a couple of keystrokes you can toggle between the two.
If you're not at your computer, you can use a program like Twittelator Pro that lets you switch accounts from within the program.
This way, you have the best of both worlds. You can turn on the firehose and see what everybody's doing, and check your @ replies. Then you can switch over and see what your smaller circle of friends are doing.
Sorry if I put you in suspense for such a simple idea. But if it works, by all means. If not, just send it right back...
(Disclaimer: Let it be known that I do not endorse breaking Twitter policy. I just looked and couldn't find anything in their FAQ's about whether you're officially allowed to have multiple accounts or not. If it's not allowed, then please ignore this post!)