I haven't played Rifts in about 10 years, so take what I say with a grain of salt, but . . .
Rifts needs a strong-willed GM with a clear idea of where the campaign is going and a solid knowledge of whatever rules the party chooses to use.
Rifts also needs a group of PC's with similar interests in the type of game they want to play.
These rules may apply to other games, but IMO, apply trebly to Rifts. As noted above, the core rulebook alone contains rules for creating ordinary run-of-the-mill vagabonds, gigantic super robots with an effective weapons range of more than a mile, or a damn dragon. If player "A" expects a gritty game of post-apocalyptic survival, player "B" wants to be a heroic mech pilot, and player "C" wants to be a werewolf struggling with his dark side, they can all do that. And, in my experience, trying to do all of that at once leads to an unsatisfying game. Try to decide the tone you're going for immediately, and require the players to create characters that fit that general tone.
Also note that the Rifts ruleset is wonky. Some rules don't make sense as written. There are a lot of little subsystems that use different rules from each other. (Magic, in particular, seems to be a collection of ad hoc subsystems created without reference to each other.)
Character creation and NPC generation can take a looong time.
I dug on the system for awhile, but found it to be a lot more work than I was willing to put in. Also, I had moment that might qualify for the "worst RPG experience" thread, which was unrelated to the system.