You could have a a disk problem try running Apples Disk Utility application to verify the drive. To make repairs you will need to boot up under an external drive to allow the app to fix the drive. Make sure you have a good backup before doing this of all your important data.
The second issue you could be facing is a full HD the problem here is the OS not being able to find contiguous blocks to use. First see that you have at least 12 - 15% of free space. If not I would start by deleting as much junk as you can.
Even after freeing up space this freed space won't be in contiguous blocks this is where a defragmentation tool is needed. Sorry to say Apples Disk Utility doesn't do this, you'll need to get a third party tool like Drive Genius (which I use). In any case before you defragment your drive again make sure you have a backup of your files, then run Apple's disk utility from an external boot drive to verify and repair your drive in case you have some low level problems or use Drive Genius' drive repair tool.
As a side note: I defragment my personal HD's yearly and some of my offices drives get it twice yearly.