As with a lot of topics in Las Vegas, the answer is probably "it depends on what matters to you". Here are the places I've stayed downtown.
If hotel amenities are important to you, then the Golden Nugget is your best choice. I haven't stayed there in quite a few years. I'm not a high roller and I'm not part of the younger, trendy set they were trying to attract. If amenities are important, I think the GN is actually a very good value. Even if their rates are high by downtown standards, a comparable hotel on the Strip, much less in any other tourist destination, would cost you much more.
Main Street Station - good offers/ good VP especially at the bartops. Friendly staff. The only real con I can think of is that at first glance, you'd say there aren't many restaurants, but since you can charge meals at the Cal to your room and maybe get them comped when you check out, you actually end up with quite a few choices for food. And for casual dining, 777 is one of my favorite choices anywhere in LV.
Four Queens - very good offers and again good VP. I know there are folks with mixed opinion of both Hugo's and Magnolia's. I'm not a foodie and I typically don't get adventurous when ordering food, but I've only had one bad meal at Magnolia's and none at Hugo's. I really like the IPA at Chicago Brewing Company, too.
El Cortez - I don't mind the walk between there and FSE at all, even at night. I'll qualify that by saying that I rarely make that walk after midnight, but now with all of the lounges between FSE and the EC, I'd feel safe anytime. They're cleaning up that district very nicely. I enjoy both the Flame and the Cafe there and the offers I get from them are nice. The fitness center at the Cabana Suites is very nice, especially since you can look out the window at that apartment complex and check out all the drug deals, prostitution, and who-knows-what-else is going on in broad daylight. The closest thing to a con for me is that they only have 9/6 JOB in multi-strike. If they had that on the bartops, it might be the only place I stayed.
Las Vegas Club - I hadn't stayed there in several years until this summer, when I finally decided to book at their absurdly low rates for a couple of nights. They gave me a North Tower room, even without my asking or using the $20 trick. I went in expecting the worst and was very pleasantly surprised with the room. And they have lots of 9/6 JOB, which they didn't have back in the old days. If you only need a place to sleep a few hours and take care of the necessities, it's fine. The only real drawback is the lack of choices for food. I also got a nice comp to Tinoco's Kitchen, which was very good.
Sorry, I know you asked for one choice. If I had to give one, I'd probably lean towards the 4Q, only because their offers are the most generous.