I tend to forget about taxes in July and October, so I've learned to pay estimated taxes in April (of the year before) and Dec/Jan (when my information is more accurate). I suspect my 12 month in advance payment has the biggest impact - lowers the penalty the most.
This looks like an unpredictable year, so I'll probably pay 2/3rds of my estimated taxes now, for next year. You can play with tax software to see how the estimated penalty changes based on when you make the payment.
In my experience, the safe harbor provision tends to work well when you're income is going up, but not be useful when it drops suddenly. So I just go with 2 estimated payments a year - not according to how the IRS wants it done, but certainly lowers the penalty enough to stop caring.
Also search for "IRS direct pay" (don't trust IRS links from strangers!) to see how you can schedule an IRS withdrawal online, from your bank account. Once it's setup, it's fairly easy to do. I mean, except for getting the money together and watching it go...