I'm using a Logitech Harmony 650 that I bought from BestBuy recently at a slight discount.
Basically it does the job but also has had one problem with batteries making contact that other people here have reported. I read of various problems with them so when I bought it I also bought the BestBuy extended warranty.
It took a little doing to program it, mostly because I didn't fully understand its different methods of switching inputs. I'm not completely through tweaking it but we use it now and put away all of the other remotes. I first tried programming it through their website interface. I didn't like that so I downloaded their program that installs on my computer and reprogrammed it that way.
Right now I have a cable DVR, a BluRay player, and the TV itself. Most of the time we watch using the TV tuner with our cable connected directly to the TV. I watch a lot using the DVR, and once a week or so we watch a DVD or BluRay. I didn't mind using the various remotes but my wife didn't want to take the time to learn it all. She had written down the instructions for switching the TV from one input to another, when we bought our new TV I had to rewrite the instructions for her. I intended to add a sound system to the TV so I figured surely I would have to try the programmable remote.
You tell the Harmony what specific pieces of equipment that you have and it looks up the infrared codes from the Logitech online database. However there were a few buttons on my LG BluRay remote that it didn't have so I had to teach those to the remote from the original remote. Another thing that the remote does is to remember what devices you are using, and what it turned on and turned off. If you pick up the remote and push the "watch tv" button, if the tv is off then it turns it on for instance. The remote has activities built in, such as "watch TV" and "watch a movie". In my case I set the "watch TV" to use the tv's builtin tuner, and the "watch a movie" to use the BluRay. I set up an additional activity and called it "watch DVR". So if I have been watching TV and I push the "watch a movie" button, the remote tells the BluRay to turn on, and tells the TV to change the input to the input that I have the BluRay HDMI cable plugged into. This takes a few seconds so you have to keep the remote pointed at the devices until it has completed its thing.
I got the remote to this point and everything worked pretty well. My wife could use it to switch devices and then it would control the devices pretty well with its buttons. The 650 has a small screen at the top and 4 buttons that relate to the screen. Depending on the devices you have set up those buttons will have certain labels and actions assigned to them by default. I have now reprogrammed mine. I looked at the remotes for my tv, BluRay player, and DVR and found the buttons I use that weren't already on the harmony, and I reprogrammed the buttons by the screen to do these functions. With cheap universal remotes I've used in the past, they would control most functions of the device well enough but there were always a few special buttons on the original remote that weren't on the universal remote. Now with the harmony I have those special buttons as well.
The last complexity I added was a sequence of commands to get my cable DVR to bring up my list of favorite channels. With the original remote I push a certain button on the original remote to bring up a menu, then I push the select button twice to get to my menu of favorites. On the harmony I set up a sequence of these 3 button pushes and assigned it to one of the buttons beside the screen. When I push that particular button now it sends all 3 button press commands to the cable DVR and brings up the appropriate menu.
So yes the harmony can be programmed for fairly easy one-button use, and can replace the full functionality of the original remotes.
There are a lot of different Harmony models available for sale new now, the difference in the cheaper ones and the more expensive ones is partly a matter of how many different devices they will control. I have a TV, BluRay, and cable DVR for a total of 3 devices. If I eventually add a sound system then that will make 4 devices, still within the capacity of the 650 model.
Other differences- the more expensive models have better screens, and some have rechargeable batteries. The cheaper ones like my 650 use standard AA alkaline batteries, and are supposed to last 1 month per pair of batteries.