Why might my mac be running extremely slowly at times?
There are a lot of possibilities, but worst thing first:

Run /Applications/Utilities/Console.app and check system.log.

Look especially for entries that say something like disk4s3: I/O error.
If you see that, see this: Hard Drive Recovery

Also look at Console Messages.  There are usually a lot of weird messages in there, but look for repeated things occurring at the same time as the slowdowns.

If the app is completely unresponsive for several seconds at a time, particularly if it is giving you the spinning ball cursor, then it is likely a disk I/O issue.  If the app is just slow, particularly if other apps are fine, then it may be trying to do something in the background that happens to involve a lot of time dependent operations (like network chatter) which don't show up in activity monitor because they mostly involve idle waiting.  

Graphics issues can also cause weird slowdowns, but that should be something obvious like having a 3D shooter (or iTunes visualization) running in the background, a second display hooked up, or custom graphics drivers installed.

Clear all browser caches, quit all unnecessary apps.

Another possibility to consider is overheating.  Make sure all vents are clear, get a Fan or temperature utility.  But now I'm really reaching.  The answer is likely in the logs somewhere.