Our use-case is different (not cassandra or db hosted on ephemeral drives), but what we've found using AWS for about 2 years now is that when an availability zone goes out, it's either linked to or affects EBS. Our setup now is to have base-load data and PG WAL files stored/written to S3, all servers use ephemeral drives, difference in data is loaded at machine creation time, AMI that servers are loaded from is recreated every night. We always deploy to 3 AZs (2 if that's all a region has) with Route 53 latency based DNS lookups that points to an ELB that sits in front of our servers for the region (previously had 1 ELB per AZ as they used DNS lookups to determine where to route someone amongst AZs and some of our sites are the origin for a CDN, so it didn't balance appropriately...this has since been changed) that is in the public+private section of a VPC with all the rest of our infrastructure in the private section of a VPC (VPC across all 3 AZs). We use ELBs internal to the AZ for services that communicate with each other. The entire system is designed to where you can shoot a single server, a single AZ or a single region in the face and the worst you have is degraded performance (say, going to the west coast from the east coast, etc.).
Using this type of setup, we had 100% availability for our customers over a period of 2 years (up until a couple of weeks ago where the flash 12 upgrade caused a small amount of our customers to be impacted). This includes the large outage in US East 1 from the electrical storm, as well as several other EBS related outages. Overall costs are cheaper than setting up our own geo-diverse set of datacenters (or racks in datacenters) thanks to heavy use of reserved instances. We keep looking at the costs and as soon as it makes sense, we'll switch over, but will still use several of the features of AWS (peak load growth, RDS, Route 53).
The short answer is to design your entire system so that any component can randomly be shot in the face, from a single server to the eastern seaboard falling into the ocean to the United States immediately going the way of Mad Max. Design failure into the system and you get to sleep at night a lot more.
