1. The core d20+mod mechanic itself. While this works fine at low and mid-levels, at high levels this mechanic completely breaks down. After 10th level the die roll becomes inconsequential, since the mod is often over 20. I'd like to see a system that scales better with level, so that the die toll never becomes insignificant.
2. The CR/EL system for determining XP. Quite frankly, this system blows and is completely subjective. I much preferred the XP system for 1E and 2E, if XP has to be handed out for killing monsters. Honestly, I wish there would be a move towards story-based and RP XP, but I know there is a sizeable fanbase for the "killing things and taking their stuff" approach. Just the CR/EL thing isn't in the least accurate, and is entirely dependent on the individual characters.
3. Classes that are too restrictive as far as skills. I think its rather stupid all fighters have the same skills, all rogues have the same skills, etc. What I think should be done (and I have done in my games), is to have a certain number of class based skills for each character that the character can choose from an available pool. Perhaps give each character four skills when they are 1st level that can come from the list, with certain skills that are "better" than others (ie Move Silently, Hide, Tumbling, etc), worth 2 skill picks. That way characters can have a little more variation without having to multiclass out the wazoo.
4. Too much emphasis in the core rules on multiclassing. I've seen this get to ridiculous levels, esp when 3 or 4 prestige classes get involved. Most prestige classes aren't needed at all, and too much emphasis is placed on playres choosing from 1st level their character development, without any consideration for where the campaign goes. I'd like to see prestige classes become rarer and wth lower entry requirements so a character doesn't have to plan 8 levels in advance for them, but have more RP requirement for them. I know that various designers have said never to use RP requirements for a balance for class abilities, but this is hogwash. Any DM worth his salt can make sure there are in-game responsibilities and drawbacks to prestige classes. As it is, there is too much meta-game emphasis placed on character development (feat selection, skil ranks, etc).
5. At least in D&D, too much reiance on magic items. I REALLY dislike the assumption of x many gp worth of magic items by level. If you don't want to run a high-magic game in D&D, you have to rework the system to make up for lower magic item levels. This isn't a hard fix, but its annoying to have to go back through the books and add in extra feats and skills for all characters and monsters. Plus, the fact that magic trumps skills and abilities makes investing skill ranks and feats in certain areas rather stupid since you can just fork over the gp to get items that do the same thing. Blah, boring. Plus, magic is extremely predictable in its effects, and with certainty of it working.