It's not really that it needs a defense so much as I haven't heard of a solid complaint that doesn't boil down to "I'm too OCD to stop pressing the button when I'm not having fun".
The main-quest normally should be the most important aspect of the game - with the best & most unique quests, missions, levels, areas, etc. Your goal should always to be, if this main quest is engaging, to be able to get through it "no problem".
The problem is when there's too much side-stuff, it can really get in the way of many things - such as direction, pacing of the story & character-development (if there is any attempt and succeeding of that), and (of course) actual fun. If there's too many destroy X items, kill X enemies, find X areas; it can get repetitive - especially if there's little else to keep the player engaged.
I have not got through Mafia 3 and its excellent story b/c there's so much side stuff here and some of these quests types & areas get revisited in the main quest - which has also ruined the pacing of getting the story to go smoothly; and the story's still great despite this. I have dropped this game, for now, b/c of this. Andromeda's issue is there's just so much side-stuff and you're always tripping over them, that even w/ its lengthy main campaign, it still feels like I'm some 53 hours in and nowhere close to wrapping any story arcs up. This game ain't even close to done, in any shape of form.
If the side-stuff gets boring or not engaging, well - one could in the old days, avoid it. I did not much for side-quests in The Saboteur, yet had a blast w/ the game and its main-quest...and was able to roll through it by mostly doing main-stuff. These days - with leveling-systems often in games now....eh, might not always be the best idea to avoid side-stuff (if the main-quest ain't scaling with you) and you actually might need to grind so you can actually have a chance in the main-quest.
Sometimes, you do need to grind on the side-stuff, so you can progress in the main-quest. Sometimes, you're even forced to do side-quests before you can even do a real main-quest. While games like Freelancer did this, they never did it at a pace that made you feel like "Yeah, my character/ship is not leveled-up or equipped enough" to tackle the main stuff, when it's time to go take on main-stuff. When they fail at that quite of pacing and fail at tying side-quests (especially meaning-less ones) too much into the leveling-scheme, now I have to grind to get somewhere, even though I don't really want to.
I never completed Batman: Arkham Knight at 100% completion; and I doubt I'll ever reach 100% in Shadow of War (especially since SoW looks like a AC game with Orc-killing in it; and b/c SoM felt like Batman combat mixed w/ AC gameplay, open-world, and quests...so I'd expect SoW to do "more of the same") - so I'll never experience the "true endings" from "earning them" as the dev's & publishers want, hoping I spend money on loot-boxes and what sounds like a purposely padded-the-hell-out kind of game. Two different companies, both in-bed with WB.
I'm calling this now: I see this as just the start and tipping of the iceberg, expecting more greedy AAA companies like EA and Activision might go this route w/ making these interlaced systems of $$-loot boxes, micro-transactions, padding-out open-world games, and hiding endings behind padded-out games just to get the player to spend more time and money with a padded-out game.