I'm rather confused to hear people are having targeting issues. Sometimes on a gamepad I do experience pressing "X" or "A" (yup, xbox controllers are a usable thing), and it clicks a target no where near what I wanted, but then I press "O" or "B", and try again. 9/10 times, it works how I want the second time. This has been such an easy solution for me over the years, I never knew people were having a problem with the difficulty of pressing the button.
I could see the issue if people changed the configuration...but I'm almost completely positive even with everything "targetable" "F12" "X" and "B" focus npc's and objects first, not players. Don't know what you've done to your settings, but sounds like it's something that is not helping you. Probably try going back to default, and see the joys you've been missing.
Issues with targeting in the newest dungeon? If you're on a gamepad, with L2/R2 held down, pressing L1/R1 will change targets (default, though you can change that). Dunno if it's because I've been a tank all my life, but it's become the norm to swap targets that way for so long that if I accidentally target something I don't want to, I simply grit my teeth and try my hardest to press the button again. It can be rough, but I've found that continuing to press buttons has led to a continuation of my life more times than I can count.
Sarcastic belittling aside, if people are having other targeting issues I'm happy to help, I am rather experienced on the topic.