I like a significant milestone every time we accomplish something (wrap up a short-story). So usually about every other to every three sessions. If we're still running from the bad guys, not done investigating, etc. then no milestone.
I like a major milestone every time the plot really hits a climax. That is, if there's a denouement session (like a monster of the week) or a major shift in group goals.
Finally, I don't really like minor milestones. I figure they can be rolled into major milestones. Although we tend to use a "play with it for a session, make any changes you want, but you're stuck with the second one. Revise at the next sig or maj milestone, or when we introduce a new player to keep everyone on the same page."