No doubt, hardest 
You can kill as quick as lower difficulties (with good stuff. But now after one run, you know everything or almost), but you can die much faster (especially at the beginning).
Little example : In "The Rescue" (first quest), rather than rushing weapon in hand (pretty efficient in lower difficulties), you may have to try to distract/knockout as many scavs as possible before launching the assault. On pain of dying quickly
You can kill as quick as lower difficulties (with good stuff. But now after one run, you know everything or almost), but you can die much faster (especially at the beginning).
Little example : In "The Rescue" (first quest), rather than rushing weapon in hand (pretty efficient in lower difficulties), you may have to try to distract/knockout as many scavs as possible before launching the assault. On pain of dying quickly
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Highest difficulty is the only way to go, but even on that the game might become way too easy as soon as you reach higher level and access to powerful tools.
"WHICH DIFFICULTY LEVEL FOR SECOND PLAYTHROUGH"
If you go for hardest, stealth is key. Upgrade Ping quick as you can. You'll need it. Make sure you can open doors, as a lot of gigs know a shortcut or secret alternative entrance which can save you a lot of time and trouble and frustration. Hack vending machines, screens and other things to distract enemies. Use blind attacks too.If you're not too familiar with the city, would try Hard difficulty before Hardest.
The game become quite easy near the midpoint, but the balancing sometimes is all over the place: if you don't min/max or stuff like that, some enemies will still one or two-shot you even on max level, but they'll pretty much always fall with one bullet or two from your part too, even on max difficulty. I say, go for the highest setting, you can always change later if you don't like it.
Forgot to tell you, ever since patch 1.2 there seems to be this mechanic, that makes the entire enemy group go into caution state whenever you use Breach Protocol and/or Ping. Also, cams made friendly by Breach Protocol, are temporary, and turn normal after game reload.
Nope, it's only the case if you have legendary cripple movement or legendary weapon malfunction equiped on your Cyberdeck
All the other ones (and epic or lower version of both) don't affect Ping or Breach protocol and obviously don't alert enemies.
(I don't know why, but it's probably a bug)
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Oh, okay. Didn't know that. Thanks a lot. Was still monitoring when it occurred as it sometimes did, and sometimes not. However did you find that out?Nope, it's only the case if you have legendary cripple movement or legendary weapon malfunction equiped on your Cyberdeck
All the other ones (and epic or lower version of both) don't affect Ping or Breach protocol and obviously don't alert enemies.
(I don't know why, but it's probably a bug)
First day on 1.2, very simple, I try by equiping all my legendary QH one by one with breach protocol and ping
(For stealth, enemies alerted with only Ping was annoying as hell)
And for stealth at start (if you choose that) :
Overture with silencer for headshot bonus (uncommon crafting spec available from Wilson with few 24H wait), Ping, Optics reboot and mass vulnerability are your (very) best friends. For avoid facing 3 or 4 angry enemies (could be bad at the start).
Was gonna say as it's reproducible, and you suspecting it being a bug, should report it to Support. But please, don't report it. Wanna keep using it, as I find it exceptionally challenging and immersive. Only need to take heed to do Rhino first, and then the guy upstairs.First day on 1.2, very simple, I try by equiping all my legendary QH one by one with breach protocol and ping
(For stealth, enemies alerted with only Ping was annoying as hell)
Always take very hard - everything else is just lol. And even on very hard most of your encounters become a piece of cake at 15-20+