The Realms have never really done a lot for me, mostly because the RPG material seems to be set at the least interesting possible times. I ran a campaign during the Time of Troubles back in the day, but the lion's share of material was for the new status quo after it. Similarly, the Spellplague could have been an interesting time to run a campaign, but the material was set later enough so that most of the interesting stuff had already happened.
I can't speak for the 5e Sundering adventures. Maybe they're actually dealing with the topics of the Sundering, which would be a nice change of pace.
But, for my part, I'd prefer to run adventures where the most interesting stuff is happening rather than adventures where the party just missed it.
So I guess my answer is "During any given Realms-Shaking Event."
Cheers!
Kinak