If all of your tax payments throughout the year are in the form of tax withholding, there will be no penalty if you meet any one of the safe harbors because, as Bsch4477 said, income and withholding are, by default, treated as received and paid evenly throughout the year. However, if some of your tax payments are made as estimated tax payments, these are only treated as made when actually paid to the IRS, so your tax payments will not be treated as made evenly (unless the estimated tax payments are all the same for each quarter) and could result in an underpayment for one or more quarters. For example, even if you meet the safe harbors, if all of your tax payments are in the form of a Q4 estimated tax payment, you would have underpayment for some earlier quarters unless all of your taxable income was received only in Q4 (which you would have to show by filing Schedule AI of Form 2210).
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