|The main difference when you run in safemode is that it doesn't boot up any background software or none windows Drivers. Or at least it's not supposed to.|
Seems like you may have a bunch of applications running in the background and it's eating up your CPU/RAM.
Go to start and type msconfig.
When the box shows, click the startup tab.
In there, uncheck software you think could be eating up pointless resources. Like you may have applications that you don't use often but they are launching in the background.
Don't uncheck all, the reason is because you have updates, anti virus software etc. Things that you'll want to keep running.
If you unticked a bunch of stuff, Apply then restart your PC and see if there's a difference.
Disk defrag and cleanup should help a little too, they're explained on the link i posted above.