Bookmarks and links
You cannot link a framed page properly. If you link the whole page, you will most times get to the home page of the site. You won't get to see the page you're really interested in. If you link the page itself, the layout and links of the page are missing. You will end up with a crippled page.
Frame busters
Some web designers use javascripts, that will load the full frameset, when a sub page is loaded. To show the full layout or to protect the page from being used in another frameset, hiding its origin. People have been sued over that. And that gets you the home page again. There is no proper way to link to the information you wanted to link. A real killer of the web's basic concept.
<script language="JavaScript">
<!-- frame buster
if (window != window.top)
top.location.href = location.href;
// -->
</script>
Complexity
At first sight a framed site may look simple. You don't have to repeat the navigation code, for example. It has its own spot and needs only to be put on one page. This is true for a site with a handfull of pages. But more pages need more navigation bars. When you get to hundreds of pages and dozens of bars, then which belongs to which? It's easy to get lost.
Downloading
Sometimes you see a page you want to keep, to read it again. So you download the page the subject you want is on. The entire layout is lost. If the information is divided over several frames, you will lose a part. The context is also lost, since there are no links, or at least not all of them, and probably no title.
Fragmenting
A fundamental concept in web design is the unit of information. A web page should contain a concise, complete amount of it. With a start, a beginning and an end. A framed setup breaks with this rule. The information is often divided over several pages.
Load time
Frames take more time to load than a single page. First the top page is loaded and interpreted. After that the sub pages are called and loaded. You need three or more connections to get the entire page. With bad connections you may end up with a gray area on your page. Apart from that frames themselves take your browser noticably longer to render than a single page.
Flashing
The seperate loading of pages may cause an unpleasant flashing effect. First the default browser color, then the page background color, then the background image, then the images on the page. Multiplied by the number of frames. Just a matter of taste I guess, but I don't like it.
To be or not to be
Some HTML editors put a style attribute into a frame tag by default. Several browsers don't reckognize this, making your site completely invisible. I've seen (?) a lot of them.
Bookmarks