'Aight, mystery solved. The error reoccured and after some more tracing with the respective tools it hulked up to be a failed registration-service (wasn't restarted) against an instance of the application server after a reboot.
For now we redirected the RFC-Destination to the DB-Server explicitly to avoid the not-consistently-appearing-error.
@JB, your first guess was correct after all 
Cheers, Lukas