It depends on version of ESXi you are using.
In case of ESX 4.x, snapshot consolidation may lead to an unexpected downtime as VM may be 'stunned' after multiple consolidate attempts.
It is safe to consolidate in case of ESXi 5.x as it won't cause long pause of the VM(by design).
If you can afford to downtime, consolidating when the VM is down is the best and quick way.