Hi..number if users is not the real measure of large install (we have 10,000 users on dual 3.2 ghz, 2 GB ram for a customer..they only using 50% of system resources still..i guess only 1 % using the system for pop/smtp..no real webmail use or IMAP)
Based on how much web interface is in ues, how much IMAP Is used in term of concurrent connections and amount of SPAM you get which may cause large CPU usage.
Its better to do Multi Server Install if you consider your install Large in terms of usage
Installation-Planning for Multi-Server Install - Zimbra :: Wiki
if you want to optimize single server install you can try the following:
Performance Tuning Guidelines for Large Deployments - Zimbra :: Wiki
* Small trick is to install SQLGREY.. it will save you TONS of cpu and ram which your users can use for good.
If you have problems ask here on the forums.
Raj