The software iSCSI initiator in ESX is a single instance - you cannot configure multiple software initiators.
Each iSCSI target (in the context of ESX, we will refer to a storage processor or iSCSI server as a target) may have multiple LUNs hanging from it, but will typically have a single IP address.
If you have multiple iSCSI targets, you may get some benefit out of using the IP-based vSwitch load balancing method. You would want to look at how many targets you have, and base the number of uplinks around that. In other words, if you have 2 targets, each with a unique IP address, you would want two NICs. Perhaps three, if you want additional redundancy, and you want to maintain pre-failure levels of performance.
If you have a single iSCSI target, there is no need to add to the complexity of the design with any load balancing method other than the default vSwitch port-ID based method. Here, two NICs for uplinks would be more than enough, as you would only use one of them at a time.
The software iSCSI initiator is just a software stack in the VMkernel. This software stack will communicate with the IP network just like any other application running in the VMkernel - through a VMkernel port, which is in turn attached to a vSwitch. Using the software iSCSI initiator binds your storage traffic to all of the design considerations of the ESX virtual networking stack.
Hope that makes sense,
-jk
