Is it better flying in First Class Flex (more Frequent Flyer points and a full refund) or a less expensive option (having to pay a bit for a refund and fewer Frequent Flyer points)?
That will depend highly on the airline on which you're booking, as well as your intentions. The less likely you are to cancel/rebook the flight, the more likely a less-flexible alternative will work for you.
How different are the rewards between the classes? That will depend on the airline and affect the answer.
How much is the penalty for rebooking or cancelling? That will depend on the airline and affect the answer.
Remember, too, that if you are a frequent flyer, an economy flex ticket may give you the cancellation flexibility you need, and the opportunity to upgrade to business or first class, depending on your status level.
So... much more information is required to answer the question. I'm not sure it's practical for us to address every scenario of this in a single answer.