I can't give any tips on settings, because I basically went 'Start with the Missions Seattle Season Ork Underground storyline, add own OCs, add PCs, stir, develop, go crazy, end up finishing after 52 sessions at Ares Firewatch levels'. You can grab a setting with plenty of source material if you need inspiration, or grab a place with little info if you want freedom (especially if your players are the kind to go 'but X is supposed to be Y!'
I think you'll want to go for Build Points, normal level, to decrease complexity and balance risks.
Houserules, there's a massive topic. XD
For the run-development: I take a basic idea and add some legwork description, rest is improv. I'd start with a quick campaign of say 5 sessions, where session 2 and 4 are filler, 1 starts normal but in 3 and 5 plotthreads from 1 return. Maybe the classic 'Do run, Run into complications, Deal with a framejob' storline.
Pornomancer should be banned, and ban Orgasm spell while you're at it if any player decides to come with it. >_>
Tell your players you'll want to vet the characters, to make sure they work nicely, and consider getting some feedback here.
Cut out anything you're not properly familiar with, and make clear to the players that this is to not bog the game down with too many rules. Don't take any Deckers, because they're a high Complexity factor AND slow down the game. Just let the team hire/escort one instead, when needed.
Don't allow Possession mages, because they're OP in SR4 and really hard to balance in SR5.
Stick mostly to the Core book, don't dive fully into the additional extended core stuff.