I've been pushing the consolidate behind a single instance, as long as your instance will stay under about 100k elements total. I've worked with big clients who had 150k so even that ceiling is not a hard cap, but they had to do a lot of fussing around to get there.
EOC is still a work in progress in my opinion, Right now it isn't providing a whole lot more than what you could do with a simple html summary page showing links to all your environments and pulling down some high level stats from them. You can't admin multiple instances at once from it, if you try it just sends you back into the individual instances anyway.
As long as you have latency under 2-300 ish ms between the APE's and your database/primary then there is no real need to break things up and increase your admin overhead of babysitting multiple instances. If you have teams around the world it is probably worth while to stand up a few additional web servers local to those teams, it makes it a bit faster to browse around the pages compared to running everything off the main site.
As far as licensing goes, if you have a big enough or widely enough distributed environment the ACM and NAM/NOM licenses might be a good bet, since those come with effectively unlimited APE's included. I feel like the break even point is if you think you would need more than like 6-7 APE's then you are probably better off getting those instead of single licenses, but it depends a lot on the mix of things you will be monitoring.
I know a few people who are playing the cloud orion game, but so far nobody has made a convincing case to me about why that's better in the grand scheme of things, Orion isn't the kind of application you spin up and spin down as workload fluctuate you can't autoscale it very easily (although if you get super sharp in the API and powershell you can get surprisingly close these days). If you don't already have a server presence in your remote regions then I could see some case for putting APE's into clouds, but its still kind of niche.