Size
The English Setter is a little larger on average: about 28 kg (61 lb) as an adult, against 22 kg (48 lb) for the English Springer Spaniel.
Grooming
The English Setter needs more grooming, daily brushing, where the English Springer Spaniel needs brushing a few times a week.
Temperament
They differ most on independence (English Setter: cooperative, with its own ideas; English Springer Spaniel: keen to work with you) and on intelligence (English Setter: learns readily, likes games; English Springer Spaniel: needs daily brain work).
Alike
Both are rated the same on affection: a lap or leaning dog.