I agree with Elfcrusher, while limiting stats was nice and a design decision that should be kept, the utter abandonment of tertiary stat usefulness drives me ballistic. If all fighters could get some benefits from Int, for example, we might see more niche builds around being an knowledgeable fighter rather than the more conventional variety. Maybe if strength expanded the list of sneak attack compatible weapons then every rogue under the sun might not carry a rapier. It's a big problem and I really hope they fix it in the distant future when 6th ed rolls around, but I won't be holding my breath.
I wish weapons meant something. There are precious few weapon qualities of note, and with the way the classes are structured you either use one of maybe 5 martial weapons or you don't use any weapons at all in lieu of cantrips. The weapon qualities are uninspired and have very little effect, and few set up any sort of unique approach or usage to encourage different playstyles. If we're going to give non-weapon classes viable options to select (and we definitely should) then the concept and structure of D&D weapons need an overhaul to promote some diversity and niches. To go with this...
Monster defenses are utter garbage design wise. As a DM, this is a COLOSSAL misstep in my opinion. Virtually every damage resistance in official wizards product is completely bypassed by any magic weapons. Why!? I would greatly prefer there to be some definite and unavoidable advantages or disadvantages (or even outright immunities) based on the monster's lore. Maybe slimes are impervious to bladed and piercing weapons, and resistant to bludgeoning? What if golems were resistant based on their composition? Energy types fall into this hole as well, with monsters having few weaknesses and many extrapalanar foes just getting huge sweeping resistances regardless of if it makes sense or not.
Additionally, monsters have virtually no scary options aside from damage. Level drain is gone, ability damage is insanely rare, aging effects are gone, long term conditions are gone, diseases and poisons are trivially cured, the list goes on. Rust monsters used to be universally despised because of equipment loss and especially if you have one of the aforementioned magic items they're just a joke. I can think of very few monsters the players would be loathe to fight regardless of their current level, and that's a missed opportunity if ever there was one.