Marrakesh

The answer to your question is generally the same as it would be for any European city - in the old center, you're close to all the things/reasons why you go there. The downside is that in the old center you may find more limited options for accommodations, and the good options you find may be more expensive - that's the same as anywhere.

Personally, I almost always choose someplace in the old historic center in any foreign city I visit (unless I just can't find any decent option that doesn't cost a fortune - planning well ahead is your best strategy, as the best places usually get snapped up early). On any trip I take to anywhere, the most constrained commodity I have is my time. Staying in the center of the action allows me to maximize the benefits. Yeah, one can often save some money by staying a bit further out and "commuting" in to the center, but that burns time and can cause you to miss some magical moments early/late when the places are uncrowded and at their best.

Just my 2 dirhams.

I think this is somewhat dependent on how you feel about "exotic" destinations. Are you all in, or do you find yourself wondering about whether you will cope with less-modern surroundings? There are some folks who definitely would not be happy staying in the center of a Moroccan historic district. Being on the streets there is an intense experience. If you are not accompanied by a guide, you may be constantly (and I do mean constantly) approached by young males who want to be your guide. The question is: Are you up for that all day, or do you want to spend part of your time in more sanitized (and much less interesting) surroundings?

I remember something Rick said in one of his videos. I believe he was speaking of Palermo, which is considerably less exotic than Marrakesh. He said (paraphrasing) that when he was visiting a challenging destination, he really liked having a confortable hotel room to retreat to--or words to that effect.

Unfortunately I haven't been to Marrakesh but I would not put it under General Europe because it's in Africa. Beyond Europe would be more appropriate. I think the answer to your question is not specific for Marrakesh, it's probably the same with every other city.

I think the medina areas in Morocco are rather different from Europe, at least the parts of cities tourists get to. And I've been to Marseille and Palermo. Also Naples and Genoa (though only briefly).

In Marrakesh, the old city or "medina" is more than the souks around Djamaa el Fnaa. The Medina is actually a collection of neighborhoods with their individual characters. The Telegraph had an article on Feb 15 which explains each and gives hotel suggestions "Where to stay in Marrakech: hotels by district". Worth Google-ing. I would probably stay in one of the mid price riads in these neighborhoods...they look beautifully restored, and some are family run.

But, then, I've lived in Calcutta, traveled alone in the Sahara, and more...but I still recall Marrakech as one of the most daunting experiences ever.

acraven is absolutely correct, any foreigner (man or woman) is subjected to young males insisting on following you on the pretext of being guides. While these followers will normally wander off as you enter the expat or large hotel neighborhoods, I don't know if you will be so lucky staying in some of the Medina districts.

acraven also raises a good point about hotel as sanctuary...if this is your first trip to North Africa, you may want a home base that feels somewhat familiar.
There is some good guidance in the Telegraph article I recommended.

I want to add just a small dissenting note to the cautions above about hassles from "touts" in Marrakech...

Yes, Morocco has a bad reputation for this. But in my experience, the situation has improved dramatically over the past 20 years.

My first trip to Morocco was in the late 1990s. I was solo, backpacking. I'm very white, an American, and I really stand out in places like Morocco. The touts were all over me. I couldn't walk three paces without multiple would-be guides approaching me. "Friend! You need guide!" If I mumbled an apologetic "no, thank you" or if I shouted an angry NO!! LEAVE ME THE F**K ALONE, A-HOLE!!!" it didn't matter. They persisted. If I ignored them or looked like I didn't understand, they cycled through a dozen different languages (I heard English, French, German, Russian, all sorts of things) they kept at me. It was an real annoyance.

Fast forward to a more recent trip, about 5 years ago. This time, with a bit more gray hair and a spouse tightly clinging to my side (and more money), I was prepared to ward them off. But to my surprise, I was mostly left alone. I was later told they passed a law against hassling tourists, and the police were actively looking for young men who were being pests. The difference was dramatic. Once in a while I still heard the calls of "friend, let me practice my english and show you the medina!" but they were furtive, not aggressive, not persistent. It was no longer a headache.

Morocco still has a bad reputation for touts. I'm not sure it's still deserved. I would not let this keep anyone away. I get more aggressive pan-handling from the bums 2 blocks from my house in Seattle. YMMV.