I have had some success using the terminal command top. Much the same results as Activity Monitor, but I can slow down the update speed, and sort on any field.

In my experience, the problem is usually with individual programs that fail to free memory. You will see the memory for that process creep up. See 'man top' for details about the various fields that top reports. Firefox is notorious for this, and with 60 or so tabs requires a restart every few days

If you want to dig deeper, vmmap can give you the status of pages owned by a particular process.

Be warned: sometimes slowdowns are CPU related. Sometimes disk i/o related, althoth the latter is less common with current memory prices.