1. In the beginning, I spent a lot of time on the global timeline. Yes, it's kinda a dumpster fire initially, but it becomes more useful as you build up more off-instance followers. Signal-to-noise is never great, but it's a place to start.
Follow anyone who says a couple of interesting things, or who otherwise looks interesting. You'll probably unfollow a lot of them within a few weeks, but it helps improve the off-instance signal-to-noise.
2. Boosts are your friend! Whenever I see a toot boosted that I find interesting, I click through to look at that person's profile. If they have a good number of interesting toots in their personal timeline, I give them a follow.
This approach becomes particularly useful once you find a couple of folks who reliably boost other people you find interesting.
3. Twitter is a mess, but that doesn't mean you have to throw the baby out with the bath water. Use bridge.joinmastodon.org to find folks you know on Twitter over here. If you see anyone and think "I really miss their tweets", give them a follow.
Don't be surprised if most of the accounts you find this way are dormant. But some won't be, and those tend to be worth it.
(This is how I discovered infosec.exchange, one of my favorite non refactorcamp.org instances.)
4. Finally, look for who boosts/favs/follows you, take a look at their personal timeline, and give them a follow if they look interesting.
This approach probably works best if your a prolific/interesting poster... Which I'm not. But even so, this is how I've found some of my favorite off-instance people.
Remember: Mastodon moves more slowly than Twitter (network-wide conversations seem to have a much longer tail), and there's no algorithm to suggest people/toots to you (overall I think this makes interactions/relationships more stable, but it does raise the barrier to entry).
It took me a few months before I started to find my home timeline consistently interesting. But now that it's there I find the discussions I have/read on Mastodon far more rewarding than what I have on Twitter these days.
@aRandomCat YMMV, but here's some folks who I think say/do interesting things, or boost interesting things, or are involved in conversations that I find interesting:
Mastodon instance for attendees of Refactor Camp, and members of various online/offline groups that have grown out of it. Related local groups with varying levels of activity exist in the Bay Area, New York, Chicago, and Austin.
Kinda/sorta sponsored by the Ribbonfarm Blogamatic Universe.
If you already know a few people in this neck of the woods, try and pick a handle they'll recognize when you sign up. Please note that the registration confirmation email may end up in your spam folder, so check there. It should come from administrator Zach Faddis.