no, not really. some will claim otherwise but for the most part it doesn't matter.
4 knots = strung with 2 pieces of string, one for mains, one for crosses.
2 knots = strung with one long piece of string.
Generally, 2 piece (4 knots) is considered easier to do.
can you tell a difference otherwise?
Microgel Radical MP (5), Cheap 16g Gut/ RedDevil 1.19 - 56/54# (among other setups)
Gamma 6004/WISE 2086