Windows drive letters A: and B:
I believe that it probably has more to do with legacy then it does moving forward. Despite the fact that A and B were taken and C became the default hard drive assignment, most applications assume that C is the default OS location, A and B are floppies, and D is CDROM or DVD drives.
I've seen applications break if the default OS is not located on C.
Some (badly written) software, including parts of Windows assumes that the OS drive will be C, and will crash/fail if this is not the case. Microsoft doesn't want to break stuff, so they've left the default as C.
When I built my last home machine using Vista, I tried to use A: & B: for the CD-ROM drives. I forget all of the problems with that I encountered, but Vista was clearly not amused.