The most important tweak for your Microsoft Server running Exchange 2010.

In Microsoft's infinite wisdom, they decided to have the Exchange software hoard every free speck of RAM on it's host system in an effort to minimize pagefile use and speed up end-user experience.  The result in reality is a system that struggles to keep up with just about any application, including the mail system itself.  The fix is fast and fairly simple for those with some decent IT knowledge.

To determine how much RAM to let Exchange play with, an easy formula I use is 66% of total system RAM for multi-role servers, and 75% total RAM for servers dedicated to the mailbox role.

1) Start the server's ADSI editor
2) Navigate to Configuration > Services > Microsoft Exchange > <Organization Name> > Administrative Groups > <Administrative Group> > Servers > <Server Name> > InformationStore
3) Right-click InformationStore, and edit msExchESEParamCacheSizeMax. Set it it to the number of pages to maximize the Database Cache to. (Pages = M x 32768) Where "M" is the number of GB's of RAM you want to set aside for Exchange.
4) (only necessary in Exchange SP1 which you SHOULD be using!) edit the msExchESEparamCacheSizeMin parameter and set it to 256.
5) Restart the Microsoft Exchange Information Store service for the change to become effective.