Berlin - stay by Humboldthain park or the Ostbahnhof?

There is a case to be made for either area. Around Ostbahnhof there is a lot of nighttime activity along the Spree and although it's a bit out of the center, the train station makes coming and going easy.
On the other hand, Humboldhain Park is a nice area, close to many attractions and also easy to get around. With so much great transportation in Berlin, my take is find the best place to stay wherever it happens to be and then go where you want to. Around OstBahnhof, make sure the bridges are open if you plan to travel by bus or taxi.

which is better ...

For your criteria both areas are good. Ostbahnhof is located at the main train axis and so you can be within 10 minutes in the center areas or back in hotel. Humboldthain with close Gesundbrunnen is part of the S-Bahn ring which is no real help for tourist because it does not lead into the center - for this purpose you can use U8 to Alexanderplatz but then has to change into S-Bahn axis.

Since I lived in the area for over 10 years I can say that open bridges were not really a problem because nobody can close them. Of course a demonstration can block it for a few minutes but that's it. The nightlife around Ostbahnhof you will not recognize because most of them are in closed buildings.

Around Ostbahnhof you will be closer or directly at some sights like East Side Gallery, Stalin's bathroom, river Spree cruises and a few others.

So, open choice - no restrictions.

Where at Ostbahnhof?

I am only familiar with Ostbahnhof having stayed there several times, the last occasion in 2023. I like staying there, a very good and convenient transportation S-Bahn hub.

The Intercity Hotel Ostbahnhof can be accessed directly within the station. On the bottom floor is a convenient Reve. The station has been refurbished, etc. obviously. I first saw Ostbahnhof in 1997, quite different then.

There are hotels on Strasse der Pariser Kommune. Staying in Ostbahnhof will give you quite a different impression of another area of Berlin.

At Ostbahnhof newer are Hotel Schulz, Moxy and Hotel Amano East Side. Hyatt's Me and All Hotel will open this year in building of former Ibis Hotel at the waterline.

I have a very large amount of points with Marriott, and they have offered a really good rate for 4 nights at their Moxy hotels in Berlin. In this case I'd prefer to stay a bit outside the city center (I usually do, no matter where I go) because it gives me some feel for the city outside of the normal tourist vibe.

I like the connections via Ostbahnhof, but the park also has an attraction, especially with the longer evenings we have now. I only have plans to see the Reichstag and everything else is up in the air, but I'll have 4 days to look around a city I haven't visited in 30 years.

I just made a reservation for 2 nights Hotel Brandies in Munich. It got good reviews. Smaller maybe older hotel..not in city center. We usually prefer non brand more family run hotels. I think this is? Hope its not too out of the way and its ok??

Points stay! I love using points, it's like being able to spend the same money twice, even better if it was work-trip paid points.

There is kind of an extra challenge with it, though, isn't there, it's a little bit backwards from conventional, not where do I stay, but which of these specific choices serve me best within these limitations.

When I'm evaluating points hotel stays I always use Google maps with imagery turned on, and then streetview and "walk" a block or two. I also then read the Google/booking.com (if available) reviews, as opposed to ones on the hotel website.

I didn't take the time to read reviews, but I did look at streetview. The Moxy Ostbahnhof is basically absolutely next to the tracks and 90degrees from the front of the station with an unimpressive platz in front. It looks to be brand new. Other than the train station, there aren't many restaurants or anything very interesting around it. Humboldthain is also reasonably close to a station but it has a large park with playground in front, and seems to be part of a neighborhood with many more restaurants, pedestrians, services and a busy street. The building looks a bit Art Deco-ish and is smaller as well.

You're sounding like you're wanting an unstructured "see what I feel like doing" sort of trip. When I'm more unstructured I find it's better to have restaurants nearby as I don't plan those, either.

With the disclaimer that I'm not that current on the diverse Berlin neighborhoods and have just done a cursory look without looking at the non-affiliated reviews, I'd probably lean toward Humboldthain based on the streetview.

Things to think about, anyhow.

On restaurants in the close vicinity of Ostbahnhof: look for Straße der Pariser Kommune 18 b for "Restaurant Volkskammer"

One of the exits out of Ostbahnhof is the "Straße der Pariser Kommune"

The Berlin Ostbahnhof area is a diverse unique neighborhood in contrast to what you see in Berlin Zehlendorf and Charlottenburg. I like going there and find it on its own fascinating.