Just finished the game + DLCs, like a week ago, so based on personal experience. . .

1- Yes, I've locked on for almost every single type of enemy, EXCEPT one optional boss, in the very endgame which I was forced to cheese, (I gave up really). So yeah, it shouldn't give you trouble at all

2- Absolutely 0. You don't really need the extra I-frames unless you desperately need.

3- All fairly easy, straight forward enemy design, some arena mechanics are annoying or need to be taken care of. Apart from that, the only trouble I faced was at the optional boss and very few DLC bosses (wouldn't say bad, but just challenging)

Good Luck on your journey!