Consider using ISA for web and FTP caching scenarios, particularily if it is already deployed as an edge firewall.
Chain ISA proxy servers if it's necessary to provide faster local content caching that passes requests up to a centralized proxy server location.
For redundancy of ISA caching environments, consider the use of the Enterprise version of the software and the Cache Array Routing Protocol (CARP).
For clients in a domain environment, consider the use of Group Policy Objects to configure proxy server settings.
Use a combination of DHCP autodiscovery and DNS autodiscovery settings that use WPAD to ensure that all clients get proxy server settings.