A. Yes and no. In the early App-V days (when it was called Softgrid), the guidance was that if you had a mix of OSs, such as Windows XP or Windows Server 2003 and Windows 2000, you should sequence on Windows 2000, and it should also run fine on XP and Server 2003.
Today, you're looking at having Windows 7, Windows Server 2008 R2, and XP, and you'll often hear the same guidance—you should sequence on Windows XP and it should work on Windows 7. However, that isn't always the case. Often an application sequenced on Windows XP won't run correctly on Windows 7. (And in case you're wondering, never go the other way—don't sequence on Windows 7 and expect the application to run on Windows XP.)
Windows XP and Windows 7 are OSs with fundamental differences. Also, many applications today install differently depending on the OS they're being installed to. Therefore, even if an application sequenced on Windows XP does run on Windows 7, you might be losing functionality or enhancements that would be available if the application were installed in Windows 7 or Windows Vista.
The guidance today for sequencing is to sequence on the OS that the application will run on. If you have both Windows 7 and XP, you should create a version for Windows 7 and one for XP to ensure proper and maximum operation.
Note that one version sequenced to run on Windows 7 and Server 2008 R2 would most likely be fine, because they're essentially the same OS. Just test to make sure the application behaves as expected. Server 2008 R2 is always 64-bit, but an application sequenced on a 32-bit OS should run fine on a 64-bit OS.