Q. Which applications shouldn't I try to virtualize with App-V?

The application has a driver. You can't virtualize drivers. If it's possible to separate out the driver then deploy the driver part to the machine using traditional means, such as System Center Configuration Manager and Group Policy, then virtualize the rest of the application you can do it, but it's not always possible.

Applications that interact deeply with the OS, such as malware protection.

Applications that have services that start independently of the application at system startup or logon, such as certain types of firewall clients and malware protection. You can virtualize services, but only ones that start as part of the application launch.

Any part of the OS, such as Internet Explorer or Media Player.

Applications that have shell extensions, such as an application that extends Explorer with additional functionality (i.e., compression).

Applications larger than 4GB in size. (I can't think of any .)

COM+ applications that are dynamic in nature and can't be sequenced. Normal COM or DCOM is static and can be sequenced.