I have heard this question way too many times over the last few years and it's time to put this to bed, in the meantime I'm going to do my best to explain my thoughts on this question and we're going to do it as simply as possible.
Agents of Shield revives Phil Coulson after his apparent death in The Avengers and follows him and a new team of SHIELD agents for their encounters with unusual cases and enemies. The first season follows S.H.I.E.L.D agent Phil Coulson as he puts together a small team of agents to handle strange new cases. They investigate Project Centipede and its leader, "The Clairvoyant", eventually uncovering that the organization is backed by the terrorist group Hydra, which has infiltrated S.H.I.E.L.D. In the second season, following the destruction of S.H.I.E.L.D. in Captain America: The Winter Soldier, Coulson becomes director of the organization and is tasked with rebuilding it while dealing with Hydra, a faction of anti-superhuman S.H.I.E.L.D. agents, and a newly revealed superhuman race called the Inhumans. There are a few points in the Agents of Shield timeline where it could have branched off into another reality and we're going to discuss those further.
For starters, Inhumans have never been mentioned outside of Agents of Shield and the show Inhumans - lets just forget that even exists - so I find it hard to believe that they live in secret and not ONE Inhuman has been spotted or even mentioned in the MCU.
After Season 5 and the fall of Graviton this is where any questions of MCU continuity go out the window. In the Season 5 finale it's mentioned that Thanos is descending on Earth to initiate the snap, which was the shows way of tying into Avengers: Infinity War, however, in Season 6 the world seems to be running as normal and there is no mention of the snap or any of the effects it had on society.
Based on the two above facts, you can argue that it split from MCU continuity in Season 2 once Inhumans were mentioned, or in Season 6, when the world should be in turmoil, but it's like nothing has happened following when the snap should have occurred.
Now that Phase 4 is well underway and is tackling the multiverse the Agents of Shield continuity becomes a lot simpler. It can simply be explained as an alternate reality where the events could be playing out mostly the same as the original MCU timeline, but with a few changes. In the Loki Season 1 finale, it's explained that there is ONE timeline and all other branches are reset so that everything can play out the way He Who Remains intends. When Sylvie kills He Who Remains the multiverse is broke open, and since the TVA exists outside of time this opens up all new realities from the beginning of time. This is what make makes Spider-Man: No Way Home and Doctor Strange: In the Multiverse of Madness possible. There are infinite realities at play now and every Marvel property that has ever been released is technically canon in its own way, but not directly to the MCU.
So to answer the questions, Is Agents of Shield canon? The answer is up to the viewer, there is no concrete yes or no in this situation and it should be interpreted however the viewer wants to interpret it. If you believe its full MCU canon, good on you; if you don't believe any of it is canon, good on you; if you believe it's canon up to a certain point, good on you; as long as you have solid arguments to back up your point I couldn't care less on how you view it.
Personally, I like to think it' canon up to a certain point in the timeline and then it branches off. As mentioned above, around the time of the introduction of the Inhumans and the Age of Ultron tie-in episode is where I like to branch it off, but I can also see points where it's not canon at all and that Coulson never really was brought back to life following The Avengers.
This is my personal opinion on whether or not Agents of Shield is canon, I think it's a question that needs to be asked, but not taken so seriously. I think Marvel is doing an incredible job at covering their tracks and having explanations for everything which will get more and more difficult as the MCU continues to grow.
A Cool Nerd