The closest you come to in Oblivion is to penalize certain skills while wearing armour
Well, you could look at more than just armor, and you could go further than the small penalty in the vanilla game - maybe as far as "full armor == silenced". I do like the idea of checking attributes and having penalties in one skill for levels in others.
You already have encumbrance limiting the amount of armor a weak character can carry (and so equip). Armor gets "lighter" with skill, but weapons don't, so a low-strength mage is at a disadvantage. But with the current setup, that mage can decide to work on skills that increase his strength if he wants to do so, without being artificially "banned" by his initial choices. The levelling system could be tweaked so that "opposite" attributes couldn't be increased at the same time, but I'm not sure that would make much difference. A few skill-to-attribute relationships could be changed, so that a different attribute is increased by leveling a particular skill, but there's already a fairly good distinction between the physical damage skills and the magical ones, so you couldn't do much there. To make a real change, you'd have to start decreasing the opposite side.
Bottom line is that I'd expect any change to be either ineffective, or too effective. You'd have to go to an extreme to make any change work, and that might be too far.