It varies a lot for me. Some days, I'm so in the zone that I can draw for eight hours straight and it feels like everything is effortless and amazing - and some days, I sit there flailing with my pencil going "BUT HOW DO NOSES WORK? D:" and everything is horrible.
Happily, I have more of the good days than the bad ones.
But if we're talking specifics, I find I'm much more at ease when drawing things familiar to me. People, animals, organic shapes and curves, etc. (though I do have partial face-blindness, which means that drawing characters' faces "on model" is hard for me). Those are shapes and lines that flow easily.
It's when I'm drawing things I am not as confident at - like architecture and complex perspectives and weaponry and, like, wagons and carts and stuff - that I have to struggle and slow down and bang my head against my tablet before I manage to get it right.
It is definitely the unfamiliarity that trips me up, I know that - I've been pushing myself to draw the stuff I don't feel confident with (architecture, crowd-scenes complicated perspectives, etc.) throughout Grassblades, and I can feel myself getting better at it. Some things - like roof tiles! - will forever slow me down, because they require me to be careful and not rush, but they no longer feel quite as horrible to draw as they used to.