I think you need to work with an accountant or certified consultant to have someone explain to you how the process works and what should be verified. 

If you have a 401K or some type of cafeteria plan the numbers may not seem to automatically match up.  

Or maybe someone has a company vehicle.  All of these thinks can affect your w-2 wages and federal tax liability. 

You should always reconcile your payroll register for the quarter to what the 941 generates.   Wages on the 941 (line 2) is calculated (from the payroll register):  Gross minus any pre-tax deductions (health care premiums, FSA) and retirement withholdings.   Social Security & Medicare wages (lines 5a and 5c on the 941) are gross minus pre-tax deductions.   If you have any employees that make over $132,900 per year after pre-tax deductions, then your Medicare wages will be more than your Social Security wages.

I am having the same issue. I am only off by 1,500 though.  I found a couple of my issues when I did the W2 "test drive" wizard.  One of my employee's totals were off so I printed out her payroll register information and found part of my issues. I also looked at my audit trail for deleted transaction. Where I found and then remembered having an issue voiding a check. I check my 941's quarterly. I am currently waiting for a call back from Sage. 

If the business is an S-Corp, and the S-Corp is paying health insurance premiums for the shareholder, this could also cause some confusion between the payroll earnings and W-2. The health insurance premiums are added to gross payroll (for federal and state withholding purposes) but are not actually "paid" to the shareholder. Certain other benefits are also taxable to S-Corp shareholders (for federal and state withholding but not for FICA - Medicare and Social Security). Pre-tax benefits lower the Box 1 wages (on the W-2), but are included in Boxes 3 and 5 (Social Security and Medicare). Health insurance premiums (paid to shareholders) is included in Box 1, but not in boxes 3 and 5. Retirement contributions (paid by the employee) is not included in Box 1, but is included in Boxes 3 and 5. In most cases, Box 1 wages will be shown in Box 17(?) for state wages.

Normally, the W-2s are calculated from the same information that is reported on the 941s. Is it possible that wages were paid that were not reported corrected for the 941s? Or perhaps checks were created and coded to the wrong account(s). I have seen this happen when clients give a payroll advance to one or more employees, but they code the transaction incorrectly, and then the "advance" is not paid back to the employer (even though it really was paid back and taxes properly withheld).