is there a difference in the connection tracking if you specify a node via iRule?

I think the most significant performance impact will be in 1) the DNS request, and 2) the packet path to the remote site. DNS should normally be cached for some configurable amount of time, so that's maybe not a huge concern. As for connection tracking, in/out metrics on the server side will absolutely depend on which direction the traffic is flowing, and client side will only be affected so much as the remote request/response slows down the application experience as a whole. Connection tracking is relative to your point of view, client side or server side. Otherwise a node command is no more or less efficient than a pool command.

To your second question, this is a not too uncommon sort of thing actually. It's not the most efficient thing in the world, and is highly dependent on the latency and frequency of these remote requests, but it's sometimes unavoidable. Where you might run into trouble is in the availability of the remote service. One would hope that the remote site owner is running LTM with robust health monitors and GTM to serve up good addresses, but that's usually not the case, so the burden is on you to handle availability. You could, for example, use a pool instead that is periodically updated from a monitor script that does DNS lookups and health checks. You could evaluate the response and resend to a different IP if the response was bad (or perhaps didn't return in some amount of time). Or, hypothetically, you could consume the DNS response into a table and round robin through the IPs (marking bad responses) and maintaining persistence at the application level. You could also employ some basic caching/compression practices in LTM, or more powerful stuff in WA/AAM to basically prevent the remote request in the first place if the content is cacheable.