For an A/V receiver: yes, just the one RCA connection.
For a "stereo amp" you'd have to be more specific. For example, if it has a set of variable pre-outs you could run two RCAs, or coax cables, to the left/right imput of your sub. Or you could run a second set of speaker wire from the amp's speaker posts in parallel with the speakers, if your sub has high-level inputs. But seeing as you originally mentioned a 5.1 system, I wonder where you're going with all this. You might want to consult a custom installer, as these are fairly basic issues.
For a "stereo amp" you'd have to be more specific. For example, if it has a set of variable pre-outs you could run two RCAs, or coax cables, to the left/right imput of your sub. Or you could run a second set of speaker wire from the amp's speaker posts in parallel with the speakers, if your sub has high-level inputs. But seeing as you originally mentioned a 5.1 system, I wonder where you're going with all this. You might want to consult a custom installer, as these are fairly basic issues.