One axis is number of people actively using the tracker for a single project — I personally think that threshold is around 50 people^1. Another is workflow complexity — very few tools are as capable of mapping business processes to software as JIRA^2.
1. Careful, there's another threshold at which JIRA becomes painfully slow. At that point you either move to something that's less adequate in nearly-every way but scales or you start splitting JIRA instances by department or project.
2. Careful here as well! Poorly created JIRA workflows are probably _the_ #1 reason people hate using it. Users learn a highly customized JIRA workflow and think it's absolutely bonkers that Atlassian did this to them, when really it's their company's customizations that are causing the pain.