I use my stomp boxes sparingly. I tried using the best cables when using them but I feel that I'm still losing my clear sound. But if I must use effects, I trust my GT-8. With it, I have more control over the tone.
But 75% of the time if I can get away with it, I like the sound of my guitar plugged straight into the amp.
If you have a couple of buffered-bypass effects in the loop, then you will notice a change in tone.
Also, some of these high-end cables that say they increase mids and lows are really just lopping off your highs. Gotta love marketing

Also, about buffers, it's a great thing to drive longer cables without loss of tone, but sometimes they don't want to act right with other pedals (like a lot of fuzzes), and like stated before, once you get a few in line, it's detrimental to your tone.
There's that whole true-bypass v. buffered debate, and the truth is that they both have their pros and cons.