At the end of the War of the Second Coalition, Spain considered making a separate peace but didn't. Let's say that Spain does worse, losing a substantial bit more of their fleet, and makes peace a few months before or at the same time as Austria leaving the Second Coalition.
It seems likely that there would be little net effect on what Napoleon gains - even if he's forced to agree to a few other things he can always break those agreements - but once the Third Coalition starts, things get interesting if Spain is convinced not to join Napoleon. They could invade France directly, forcing Napoleon to keep forces back or even take care of Spain first.
I doubt Spanish neutrality would mean much - Napoleon didn't respect them as an ally so he's certainly not going to let their neutrality keep him from going through them to get to Portugal. (And, the British were unable to keep Buenos Aires so I don't know if that invasion not happening wouldn't impact things much.) Although, it's possible, I suppose, that he'd be able to invade part way and coerce them into transferring another colony to him the way they did louisiana.