Think of the opposing team's offense as a three-legged stool. You want to knock it over. Do you kick the sturdiest leg? No, that'd be silly. Kick the weak leg.
Look, marquee players are going to get theirs. You can put your best defender on them, rotate defenders, do what you want; they are still going to get open, still get the disc and still make throws. But we all know Ultimate isn't a one person game. That marquee player cannot function without the other six players on the field.
Analyze your opponent's overall strategy and look for a piece of it that you can shut down. Look for people who are doing the little things. An offense cannot run without the little things and often the people who are delivering them aren't used to dealing with the best defenders. Who is throwing the swing to the hucker? Who is consistently catching comebacks on stalling seven? Who is getting open for a reset dump? Find that player, shut that player down and your opponent's offense will suffer.