What are you dealing with? Storing DVDs? Storing DV for production? As with many things, as you get more compressed, you lose quality, so the amount of space you save depends on what you want to use the video for.
Wow, that's a very general question... Depends on what you want to go with. If you want to appeal to Windows users and not worry about them downloading a particular player, then WinMedia 9 is the way to go (although it may require a quick codec update for some). If you want to get slightly better quality, then Real 10 can be better. If you would like to stay with QT, then 3ivx is the way to go. There are a couple of other Windows-only proprietary codecs that can be better, but since this is a mac oriented site, I won't go into them here.
Basic list for mac encoding and achieving the best results:
Format / codec / encoder app / mac player required
.wmv / WMV9 / Compression Master 3 / WMP9
.rmvb / REAL10 / Compression Master 3 / Real Player 9
.mp4 / MPEG-4 / Compression Master 3 / QT6
.flv / Flash Video / Sorenson Squeeze 4 / QT6
.mov / 3ivx / Cleaner 6 / QT6
.mov / Sorenson Video 3 Pro / Sorenson Squeeze 4 / QT5