There is absolutely a difference but it depends on how much effects are part of your core tone. For out and out metal type tones with slight delay then the cons definitely out weigh the pros. I love pristine clean 80's chorus tones and thats where it shines for me. The real benefit to me is that no matter how many layers I add the notes dont trip on each other like it sometimes can in stereo. Again, we are talking heavily processed. For the EVH chorus thing it also sounds great but with the extra gear you need to add vs. just stereo, I wouldnt gig with that type of setup. For at home it can be a blast.
Having complete control can be very inspiring to dive into whatever unit your working with and go nuts!