Here's my general strategy at this point.
I'm at 545 million cps. I'm keeping 10 trillion cookies in the bank at any given point.
If I'm going to babysit the game and click cookies, I'll keep the grandmothers appeased (the cost is capped at 8^13 cookies or ~550 million cookies). The most likely golden cookie click results are the cookie instant bonus (~10% of your current cookie stockpile or 30 minutes of cookie production at your cps, whichever is lower) and the x7 cps for 77 seconds. One click of a golden cookie will net me ~294 million cookies over 77 seconds, or ~980 million for the instant payout. When cookies are appearing every couple minutes (because I bought the golden cookie upgrades), a couple golden cookie clicks will make back my loss on appeasing the grandmothers. All this assumes I'm keeping 10 trillion cookies banked and I feel like babysitting the game.
For red cookies you're wanting the ~6% chance of getting x666 to your cps for 6 seconds. For me it would be a gain of ~2.1 trillion. Which is very nice, but 4 golden cookie clicks will likely net me more cookies than relatively uncommon "Elder Frenzy".
There's lots of nice math you could do to figure out at which cps it becomes more advantageous to appease the grandmothers than just work with the red cookies. There's really no extreme downside to just relying on red cookies though, you won't be losing cookies overall with them.
I'm not sure why I spent time going though this.
(sources of cookie rates and numbers are taken from the
cookie clicker wikia site, the editors of that claim to of found the info within the game code)