Yes, the thr:in-reply-to ID can be the ID of a comment (which can itself be a Salmon with a xpost:source element that points at the ultimate source). While the protocol supports threading, recipients can of course flatten salmon in the feeds that they re-publish -- though the thr:in-reply-to element can be used to reconstitute threads as needed.
Salmon is in fact based on and compatible with AtomPub. Salmon greatly enhances interoperability and usability by specifying a distributed identity mechanism for identifying the author and intermediary involved, provides a discovery mechanism, and specifies how things should be linked together. By not requiring pre-registration or federation but still allowing for verifiable identification, it provides a usable, level playing field for all parties involved.
What else is Salmon useful for?
The payload can define any kind of message, so Salmon can be extended in arbitrary ways. It is already being used to communicate mentions to mentionees. It has also been used to signal cross-site following (by sending a follow message) or to send requests (by sending requests rather than notifications, e.g., a friend request). It is best used when there is not necessarily predefined relationship or subscription between the source and destination; if there is, PubSubHubbub may be a better choice.