Crossfire functionality is always by software, as it is the drivers that will dictate how the cards will perform in that setup. Generally, most any motherboard with more than one physical PCI-E x16 slot can run crossfire
x16 + x4 is a limitation for stronger cards. Crossfire requires both cards be equal, so on a x16/x4 mobo, both cards will be treated as being on x4 PCI-E lanes.
This would be an issue if you were trying to crossfire stronger cards, but I can't imagine a 4650 being hampered much (if at all) by a x4 slot, so if you really want to have a crossfire setup, another 4650 should be fine to add to your system, but I also second outlw6669 in that getting a stronger single card would be a better investment (like a 5670 for example)