I think like any peer-to-peer site (Craigslist, EBay, etc.) VRBO and other lodging sites carry risk, there will always be some scammers out there, but I do think that the vast majority of transactions go off without a hitch.
I do get concerned though with sending a large sum of essentially cash via bank transfer with little or no recourse if something goes wrong such as if you are just left out, or the lodging is substandard.
I also have some concern that what is pitched to be peoples private homes are usually rental agencies operating outside of any local regulations (Both lodging and safety) and probably taxes.
As such, my preference is still to deal with the smaller private run hotels where I still have some guarantees, a fixed address to deal with, and only pay a small deposit at most ahead of time.