You can see in the doco here that setting up each instance of Cassandra requires a new 'node'.
My question is - to run a cluster with multiple nodes of Cassandra on my Mac (Running Mavericks) - do I need to spin up a virtual machine for each - or can I run multiple instances (in different directories or with different config files for example)?
Depending on what you are trying to achieve you can run multiple instances of Cassandra in one Ubuntu VM on you Mac running OS X Maverics.
Normally for DB clusters you want better performance or redundancy so you want to physically separate the dbs, but there is nothing stopping you running multiple instances on one Ubuntu VM.
Given that Cassandra is Opensource, you can download the binaries and compile on Maverics (assuming you have command line tools, and Xcode installed) and that way you will have an even smaller performance hit when you run Cassandra natively rather than in a VM.