Ever have that problem with a brand new XenApp 6 server running on Microsoft Windows 2008 R2 with Service Pack 1 where not even Notepad will launch? Well, the secret is to get the right Microsoft patches and Citrix hotfixes installed, which when complete will enable applications to run again. Ran into this several times and with SP1 for Windows Server 2008 R2, you must have the patches up-to-date. Here is the list of Microsoft and Citrix updates that I install on newly built XenApp 6 servers.
KB2444328: You cannot access shared files or shared printers in Windows 7 or in Windows Server 2008 R2
KB917607: Installing a 32-bit help System 2008R2 might be required if hosting 32-bit applications.
KB2465772: An application or service that uses Winsock API or Winsock Kernel API might randomly stop responding in Windows Server 2008 R2.
After installing the Microsoft patches, install the following XenApp 6 hotfixes in the following order: (#60 should be installed first as it replaces #2 and prevents the licensing information from being deleted)
After the installation is complete you can just reboot the server and your published applications should work again. Monitor the Citrix KB article CTX129229 for any changes in the Citrix hotfix list above.