Yes, they can make a difference especially on weaker systems they can make a difference how smooth they play. I've heard that there is some picture quality issues with some codecs on some players. Sasami2k just has the nicest interface with a decent amount of options. If it ever matures it will probably become my default player. My sister has noticed that some movies play better on one player, others better on another. She is on a weak (k6-2 550) cpu though.