The answer depends on the Pokemon's base stats (specifically, the ratio between its HP stat and the defensive stat in question). In the vast majority of cases, 252/128 is superior to 4/252. However, this is not to say that you should use either of those spreads in practice.
You can easily prove optimal EV spreads using a damage calculator. Below are calcs showing that for a Pokemon whose base HP is equal to its defensive base stat, 252/128 is better...
252 Atk Salamence Dragon Claw vs. 252 HP / 128 Def Arceus: 103-123 (23.1 - 27.7%) -- 73.7% chance to 4HKO
252 Atk Salamence Dragon Claw vs. 4 HP / 252 Def Arceus: 94-112 (24.6 - 29.3%) -- 99.9% chance to 4HKO
...and when HP is much higher than the defensive stat in question, there is an opposite result:
252 Atk Salamence Dragon Claw vs. 252 HP / 128 Def Blissey: 360-424 (50.4 - 59.3%) -- guaranteed 2HKO
252 Atk Salamence Dragon Claw vs. 4 HP / 252 Def Blissey: 267-315 (40.9 - 48.3%) -- guaranteed 3HKO
However, if your takeaway from this is "always use 252 Def / 252 SpD on Blissey", then you are thinking about EVs the wrong way. Balancing EVs equally in both defensive stats is a lazy strategy that ignores realities about how you will use the Pokemon in the context of a team. In singles, Blissey almost always uses 252 HP / 252 Def or 252 HP / 252 SpD because a team of six Pokemon invites you to specialise your Pokemon. Your Pokemon don't need to be jacks of all trades (and masters of none) when you have five other team slots.