What kind of hardware do you have running?
If you suspect bad queries, look for ones that have especially high reads/long durations, as these may be potentially missing indexes (insufficient indexes), check the server/query waits to see which are the highest. For instance, high PAGEIOLATCH_EX "may" indicate issues with the disk subsystem (hardware) because it's waiting to look up the page from the disk, CXPACKETS may indicate poorly written queries (or ones that have large table scans in them), and so forth.
This is such a loaded question, what specifically have you looked at?
FYI - if you're confident that your indexes are solid and your statistics are up-to-date, then most often you can dig deeper into the hardware configuration (RAM, spindles, etc)
"Never argue with an idiot; They'll drag you down to their level and beat you with experience" ;-)