What RPG has ever established this for us? You mean content that is narratively necessary to achieve victory? What game doesn't do that? That's pretty much what a main storyline is.
Are you asking which games I think the main story more effectively leads us to discover the side content? There are lots of them. The single player Elder Scrolls games, the Witcher games, DAO and DA2, Fallout 3, and Farcry 3 comes to mind. The side quests don't have to be earth-shatteringly important, they just should mostly discoverable a reasonable distance from areas that I would find myself in anyway when following the main quest.
Right, not the first part - I was more asking what RPGs in general have basically made all side quests extensions of the main plot - none exist that I know of though I'd probably argue of any I've played, Mass Effect 3 came damn close. As much as I love all the listed games aside from Elder Scrolls and Far Cry being a shooter, the majority of RPG games contain a wealth of side plots and quests that have 0 to do with the main arc and are often out of the way - that's sort of the point in my eyes. It encourages discovery, exploration and simple "I wonder what's over here..." thinking.
Consider BG2's absurdly difficult secret boss Kangaxx the Lich - you'd never find him without going off the beaten path on a merry side quest entourage that had 0 to do with the plot. Why would you do it? To take on a powerful, unique enemy and get fat loots of course!
Why do I traipse about in DAI grabbing shards as I do secondary quests WITH relevance to the main plot (You know, like purging a keep of Red Templars, eradicating army deserters attacking civilians, etc.) - because it's a side diversion that can add an extra realm of power to my character and fat loots. And because from an RP perspective, my Inquisitor would be MOST intrigued as to what the heck the Venatori want with these shards and the temple they go to...
I really wanted to adore this game, and I DO like it very much...but yeah. There was just too much "extras". In my second playthrough, I did every "extra" quest and sometimes there would 30 hrs before I would pick up the main story again. As the extra quests (besides Inner Circle quests...but even then) didn't seem to add anything at all to the main story, I was a fair bit disappointed.
I was hoping for a ME3 type deal where you would build up points for your army or "readiness", not just getting points to "buy" the next quest (I always had WAY over what was required anyway).
There was no "end game" reward for all that stuff and the hours and hours it took to complete them only served to distract and take something away from the main quest for me and even the characters and companions. Big time bummer.
I can understand the length of time it can take completing all these side zones before diving back on a main path feeling a bit long in the tooth/strange - by the time I did Wicked Eyes, I was 3 levels over the high end cap due to having cleaned out 3 side zones completely and downing 4 dragons.
But as to the side missions generally not being related to the main thread and overall arc, there's very LITTLE of that. Mass Effect 3, despite the arguments about auto-dialogue, etc managed to maintain a pretty tight correlation between it's side quests and main arc, but then again if they had us running around exploring worlds, launching probes and mining minerals while the Reapers were kicking our doors down, we might have all yelled Bioware into a coma xD
But there's generally never really an end-game reward for side quests outside of, you know - that feeling of completion. Whether it was Fallout 2 (acquiring Skynet as a companion - great side quest. NO relevance to main plot), Baldur's Gate (Dat Basilisk dude!), Witcher (Killing or hunting down some of the out of the way enemies in the swamp) or any Bethesda game (The king of "wander around and find interesting crap" RPG territory) - side quests aren't really supposed to "affect" your ending. That's why it's a side quest - it's at best, got a tertiary/secondary relevance to what's happening and exists as a vehicle to either entice you to explore/step away from the main goal for a time OR just flat out challenge you with something that may be unique.