Technically, the only part of SS2's questline that links to the 'vanilla' main quest is that bit where you first meet Preston And Pals - and even then you don't actually HAVE to rescue them, only have that first conversation where Preston and Sturges tell you about the Power Armor on the roof. You're not required for SS2's questline to go back in and tell Preston And Friends to move to Sanctuary, can just leave 'em in the museum forever if you want.
There's other "optional content" - more Unique Settlers, mainly - that triggers based off vanilla main quest progression.