I was briefly involved in a game of Rolemaster Fantasy Roleplaying about a year ago. I got all the books and everything.
As someone mentioned the organization of the books is pretty darn bad.
No one has mentioned this, but the skill system is pretty tough to play as written. I imagine most if not all DMs use some variation of their own in order to make it workable. Especially in RMSS/RMFRP, there is a skill for almost all actions. Most skill rolls, even "easy" ones, require pretty high results to be successfull; the flexibility of the d20 DC system is not present. Characters do not get enough skill points to be well-rounded even though the Rolemaster brags about its flexibility; since you need really high skill bonuses to succeed regularly, it behooves you to spend your precious skill points on skills that are easy for your class to learn. What the skills actually do is often very vague - it seems like skill effects are pretty much left up to the DM, but this is never explicitly stated. And don't ask about the opaque rules governing herb use, which in theory is a hallmark of this system.
The magic system, although it looks very cool, tends to be clunky in practice. Low-level magic users have to spend three combat rounds just to cast one spell "safely", and then the chance of the spell succeeding is almost always worse than it is in D&D. Every time a spellcaster casts a spell there is a 3% chance for it to fumble, no matter what

The rules for spell acquisition are unnecessarily limiting, whichever edition you use. Beginning players have to be careful, too - for instance there are very few offensive spells for beginning essence (arcane) spellcasters. At first level there is only one: Sleep V. For example, one new player I played with tried to make a 3rd level Ice Mage but her character was bad because she ended up not having a single offensive spell yet!
There are some really cool things about the system, but you really have to readjust it and make it your own, almost like with AD&D 1st and 2nd edition.