They lock some neat stuff behind the side missions.

[Kashra Fall]

Enemy encounters you haven't seen. Good cutscenes and lore and boss variants that you can tell, were probably the ACTUAL bosses, but probably deemed too hard lol.

[Dregora]

I mean it wouldn't be the first time side stuff bosses are harder than the main bosses. I think that's a good design choice.

[Kannibale]

So, I just beat main boss #13, the princess. I've done every single side mission so far, and the bosses of the side missions are just the main bosses, but with higher damage, more health, and a new mechanic or two.

Either they'll have electricity / poison / plague, or they'll be able to teleport around the map. So yeah, they're harder. But I haven't been stuck on any side story boss yet, they're pretty easy for the most part, since I already know the timings.