Excluding Witcher 3 in which I did everything, IF I play an open world game, I only do the main plot.
I did it in Saints Row 3,4 and GTAV (never did a side, only 63 main missions).
I think it's easy do an open world game: just see Mordor and Mad Max.
They are pretty much big, empty sand-boxes filled with repetitive activities (Max Max is just a big desert, Mordor is located...in Mordor which is just a big wasteland), so my advice is doing only main missions. Or at least is what I do.
The only case in which I do a side is if there's some kind of story content behind it (like all sides in Witcher 3).
If I just need to clear the map from marks, I'll skip that garbage.