Optimisation for high traffic sites

Hi,

I have a few clients who have very high traffic sites. Beginning with client B, he has around 45k visitors per day. His server config is:

X3430 Quad Core Xeon 2.4Ghz 8MB Cache
8GB RAM
2x500GB SATA RAID 1

I have setup W3 Total Cache on all his WP installations but the results are not as satisfactory. The main issue arises when the traffic is at peak.

I wanted to know that would be best methods to optimise WP for high traffic sites to get more speeds and less downtime?

Also, is there any other cache plugin that I should try?