Yes! By default, PlayOnLinux creates its own set of virtual drives where it places the custom WINE version that it uses. Because of that, it is safe to install PlayOnLinux alongside with a mainline version of WINE. For example, when you install Safari through PlayOnLinux, it creates a clean sandbox where it installs all the programs and WINE patches that it needs.
Further, this approach also means that removing a program that you previously installed through PlayOnLinux is incredibly simple: press "Right click" on the "Safari 5" entry in the main menu and select "Remove."