There's a number behind every knockout pick, even if you never write it down: how likely the result is, multiplied by what it's worth to you in the league. Get comfortable with that and the "risky" upset often turns out to be the rational play.
Expected points, briefly
If a favourite is 70% to win and an upset is 30%, picking the favourite is obviously more likely to land. But if half your league also picked the favourite and almost nobody took the upset, the upset is worth far more relative position when it hits. Rarity is value.
You don't need a spreadsheet. Just ask, before each knockout pick: how many people in my league made the same call? The more crowded the pick, the less it can ever win you.