Should I guess on the GRE if I don't know the answer?

Always. A guess takes two seconds and gives you roughly a 20% chance of getting the point on most question types. Leaving it blank gives you 0%. That's free expected value. If you're skipping a question, click the middle answer choice and move on. Don't spend time trying to figure out a smarter guess. The goal is speed, not strategy. Save strategy for the questions you're actually solving.