Single or multiple Virtual Servers?

Considering the very different types of traffic I'd recommend three Virtual Servers. The HTTP service will need a HTTP profile (perhaps SSL, HTTP Compression and Web Optimisation too) assigned to it's VS which wouldn't work with the other traffic types. You could consolidate the SMB and TCP into one VS but I'd still go for two as the two applications are very different and you'll be able to tweak TCP settings such as Idle Timeouts etc. for each one individually (which I assume will be important for the SMB in particular).