Some abilities should be reserved for only the single classed character - like multiple attacks for fighters, for example. You want to be a Fighter/Magic User - you will never gain multiple attacks. You WILL advance in your ability to attack (THAC0 or whatever), but there will be some benefits to being a straight-on fighter that will be lost to you. Likewise, you will not gain all the mage abilities (maybe the ability to create magic items and create potions and/or scrolls). It's really about balance for me - not balance as it sounds like 4e has established balance - but more about balancing the desire for making every class desirable to play - not all equal, in any sense.
So I like the idea of the single classed character, so I will choose to penalize those who want to multi-class.
Oh - and multiclasses have to accrue the full experience points for every class to gain the next level. So, at 4,500 xp, we have a Level 2 F/MU, and at 6,250 we have a Level 2 F/C/MU/T. Meanwhile, the straight up cleric is already 4th level with this many xp (6,500). Not that big a deal, I guess (I just ported it out - just attain 5th level F/C/M/T at 63,500 xp - everybody else is only at 7th - except the Fighter who's still at 6th - which was a surprise to me...). Taking a quick look at the Thief class, for example, I shouldn't have been that surprised. Since progression is roughly constantly doubling (until high levels), the multiclass is going to lag only one or two levels behind the single class (it does break out at very high levels - 3,565,000 xp for 13th level F/C/M/T - whereas with that kind of xp total, a straight up cleric will be about 24rd level and the Fighter will be about 22nd level - so maybe it works okay - IF we ever get to high levels).
So I'm looking at classes with an eye toward what will make sense as single class only special abilities (with a rationalization that only single classed characters have the time to develop some skills - it's thin, but that's okay with me).
But there's also level limits.
I don't know if I'll have some upper limit. Basic/Expert suggested that 36 would be the upper limit, though the Immortal rules pushed that boundary. In practice, I'm not sure I could enjoy a game with 20+ level characters (we had 'em, back in the day, but we were powergaming/Monty Haul-ing at the time - not sure how much I enjoyed that, even then...). So, there are practical limits - and there are mechanical limits - the practical being what I think I'm comfortable with, the mechanical being some actual ceiling I might place.
And it's all arbitrary - so what do I want? Well, I want there to be some uber powerful magic out there - so probably some uber powerful magic using beings...but as PCs, I don't know.
One idea I had was that ability scores could contribute to level limits in a very concrete way. Say, attribute times 2 indicates the level limit (hmmm, very nicely fitting into the 36 level mold) - or even attribute equals level limit (off the cuff, I like that better - in order to become a super high powered magic user, for example, you'd have to somehow get smarter - VERY, VERY smart, in fact...). That would mean that everybody would likely top out at 15th to 18th level.
So, lets push this a little farther. Multiclass can only attain one-half of attribute as a maximum level - so, F/M with STR 17 and INT 15 would top out at 8 (if I'm rounding down, which I think I would) but would have to gain both F/M experience to go from 7th to 8th level, even though magic ability stops at 7th level... No, too messy. Perhaps half of the least of the attributes? Then the F/MU would be max 7th level. Or just the least attribute - 15th level in the above scenario (thus, xp progression would be the major penalty - and the special ability differences). Or something even more arbitrary like lowest prime attribute MINUS THREE or something... I'll mull this over a bit more.
So - multiclassing doesn't really seem to slow character progression all that much, so there should be some other penalties, in my mind, for the mutliclass.