In a corporate environment, its important to be able to cluster webapps so that:
a) it can be deployed on standard appserver farms (which are clustered)
b) we have redundancy and automatic failover.

If the application requires a cold standby (as is the case with Jira nd Confluence as they stand), its a major PITA.
Due to it support priorities to business-critical applications, a application that requires manual fail-over will have a downtime of anything from minutes to hours.

As I see it the issues are:

1) Hibernate Caching - can be taken care of at the hibernate level (known solutions: free and not free - customer can choose)
2) Indexing. If filesystem indexing is essential, then we need some kind of fault-tolerant index synchronisation mechanism. JMS?
3) confluence.cfg.xml Config file. Can this be pre-edited and deployed in the WAR?
4) default-formatting.properties Can this be pre-edited and deployed in the WAR?
5) Custom Velocity templates: Can these be stored in database or via webdav?