To the uninitated, telling the difference between frigates, destroyers and cruisers is difficult. However, there are three major differences: the command, the shape, and the size.

The Navy has required by law that the commanding officer of a cruiser has attained the rank of Captain. The commanding officer of a destroyer or frigate must have achieved the rank of Commander, one paygrade below Captain. In my personal experience, the officers (in general) of frigates tend to be the youngest, while the officers of cruisers tend to be the oldest.

All cruisers have two masts. All frigates have one mast. This is a historical difference, as cruisers in the Eighteenth Century and early Nineteenth Century had more sail area in their sail plan, and therefore tended to sail faster. Destroyers have either one or two masts. If it has one mast, like the DDG-51 class, it is a slanted mast, unlike the vertical mast of the frigate. If it has two masts, like the DD-963 class, the forward mast is taller than the aft mast. On a cruiser, the aft mast is the taller of the two.

In comparison of pure size, cruisers tend to have a high masthead height, with large superstructures. Their beam (width) is extremely narrow compared to a destroyer, which has a beam usually 10 feet or more wider. Destroyers also tend to have a smaller freeboard. The squat dimensions of a destroyer allow it to be extremely maneuverable as a weapons platform, while the tall, narrow, long dimensions of a cruiser give it speed, even in rough seas.

Albert Herring and Berek both correctly point out that this is a US-centric writeup. I make no apology for that. Node what you know, right? However, I feel that there is probably a similar distinction in other nations' fleets. I strongly encourage writeups from experts in other nations' ships below this.