I also have a sick azalea. It looks like it may be the same issue, and we're in similar climates.

I'm in the Atlanta area. It's a well established, mature azalea. It's trimmed, but even being trimmed, it's 5' tall. It's a pink/red one time spring bloomer. It gets probably a little more sun than you'd prefer an azalea to get, but given its size and that it's established, I don't think that's been a problem. It's well mulched with cyprus, and previously with pine needles. Evergreen.
We moved into the house in April, so I don't know the variety or exactly how old it is.

I cut a small dead brown spot from it in May or so, but in the last few days I noticed this large spot- probably 20% or more of the plant. Is there anything I can do to save the plant?

There are several possibilities. The most likely cause is a borer.

Ends of branches die when a Rhododendron Stem Borer, Oberea myops, Dogwood Twig Borer, Oberea tripunctator, or Rhododendron Borer, Synanthedon rhododendri, is in a branch. Borers only affect the portion of the plant away from the roots from the borer. If the borer is in the main trunk, then the entire plant will wilt and die. The plant can be save by cutting off the area with the borer and letting the plant regenerate from the roots. There are no conventional insecticides that will kill stem borer larvae once they are inside the branches. The best control option for homeowners with only a few plants is to prune out and destroy wilting branches in early spring or late summer.

The other less common problems are all dieback diseases that harm plants that are being stressed by drought, pruning, moist conditions, etc.:

1) Phytophthora cactorum causes the central vein of a leaf to turn brown and the discoloration extends to the petiole on tender new growth. The infections spreads outward from the midrib tissue and the leaf wilts. Infections are more severe on azaleas. Control of the disease is difficult. Since the infection goes from the roots to the tips, when you see the symptoms it is too late. To prevent it, use a raised bed with lots of sphagnum peat moss. Also, keep the mulch back 2 to 3 inches from the stem. Prevention with fungicides and careful control of exposure to high humidity may be practical.

2) Botryosphaeria dothidea causes leaves to turn dull green and then brown and roll and droop. Cankers form on branches and may girdle the branch. This is the most common disease of rhododendrons and azaleas in the landscape. A typical symptom of this fungal disease is scattered dying branches on an otherwise healthy plant. Leaves on infected stems turn brown, then droop and roll inward. These leaves often lay flat against the stem and will remain attached. The pathogen can infect all ages of stem tissue through wounds, pruning cuts, and leaf scars. Heat, drought stress, and winter injury can increase disease incidence. Cankers on branches can gradually grow through the wood until the stem becomes girdled. Diseased wood is reddish brown in appearance. Discolored wood viewed in longitudinal cross section often forms a wedge that points toward the center of the stem, and the pith may be darker brown than the surrounding wood. Sanitation and applying a fungicide such as metalaxyl (Subdue) after pruning my provide some control. Plants should be grown in partial shade, with mulch and kept well watered during dry periods. All dying branches should be promptly pruned out in dry weather and all discolored wood should be removed. Plants should also be protected from rough treatment during maintenance activities to prevent unnecessary wounds.

3) Phomopsis rhododendri symptoms vary from leaf spots to chlorosis and then browning of leaves which then wilt. Browning streaks extend down the stem to a wound. Fungicides such as metalaxyl (Subdue) should control an outbreak. Sanitation and applying a fungicide after pruning may provide control.

4) Rhizoctonia solani: causes small necrotic spots on leaves, which later become dark brown or black. Defoliation follows severe leaf spotting. The fungus is omnipresent in the soil and appears to be most virulent at high humidity levels. Microscopic examination of roots and crown are the surest diagnosis. Cultural practices to control this disease include improvement of drainage and avoiding excess irrigation. It seems to only be present in irrigated beds such as at nurseries.

Thanks Rhodyman!
My particular azalea is right next to a dead dogwood that I recently dug out. I also have a few other less than healthy dogwoods in the yard, so I'm guessing option A)Borer, is my problem.

Here's the course of action I will take. Please correct me if this is off base:
-Right now, I will cut out the dead section, and destroy that section.

-In the spring, after flowering, I will follow suggestions in the Drastic Prune thread, and cut the plant back to about 12 inches, or below any foliage. I will also dispose of, rather than mulch that pruned foliage.

If the problem is a borer, would that do it?

Thanks

The pruning is not necessary for the borer. The eggs are laid in the spring or summer, so if you cut it back, they can just lay the eggs in the part of the stem that is left. They prefer woody stems. When the borer damage is first apparent (one branch starts to wilt), you can spot where the egg was laid by looking for a hole in the stem below the wilting leaves. Then you can run a wire up the hole that was created when the egg was laid and kill the borer that is tunneling up the center of the stem. It is easier just to cut the section with the borer off, but if you want to try to save the branch first, you can try the wire trick.