What compression software are you using? Are you married to QuickTime or are you willing to explore other multimedia compression options? What do you consider a "large" file (I ask this because I have found very different opinions!)?
You may want to check out the Canopus Procoder software which will give you some of the best options for choosing just about any Codec and compare quality vs. file size. http://www.videoguys.com/procoder.html