I voted for "Combat Speed", because that is by far my biggest issue with 4e.
However, for me the biggest issue is complexity. For some years, I've been finding the math of 3e to be more and more of a chore - I love playing the game, but dealing with all these irritating little modifiers all over the place is a major hassle (even in a Core Rules Only game).
Meanwhile, the other D&D DM in our group has just moved his FR game away from 4e because of the sheer weight of the rules - he got sick of dealing with themes, and classes, and races, and feats, and powers, and... That was a major shock, as previously he had been the biggest booster of 4e that I knew.
So, with 5e, it's really important that the game not become any more complex, and indeed it should aim to become significantly less complex. (My rule of thumb - if the game can't be boiled down so that everything you need to run a satisfying campaign can't be fit into a single 250ish page book, it's too complex.)
And that's a really tall order. Worse, since modular designs are inherently more complex than the same game with the options "baked in", it's even more of a challenge. I wish them every success... but I'll be astonished if they pull it off.