Also depends on what version of M2M you are operating with. V6.0.x is running with quite a bit of Visual Foxpro (VFP) code for the forms and reports. It interfaces with VFP tables that have been upsized to MS-SQL server but much of the behind the curtains in V6 is still VFP. - An issue as Microsoft stopped supporting VFP in 2009.
M2M V7 is still using VFP but not as much. Their next major release is due out at the end of 2014 and support is saying there are no more VFP hooks in it. That's great for performance, bad for continuity. This means any code, custom form, and many of the reports will have to be recreated - (not to mention the data migration). A side note, the licensing issue in V6 is concurrent. They have structured it to allow terminal services on the floor, on multiple shifts. In addition, shop Floor Manager has no license limit.
I have looked looked into upgrading to the latest and greatest, and am not convinced that I want to stay with M2M. Odoo (OpenERP) has made some solid growth in their application, and as long as we are going to have to clean up the mess that is V6.0.x I'm leaning that way.
If you are looking to just keep the monster running - look at a utility called SQL Check. It can show real time performance and show you some processor/disk/memory hogs.