Short Santiago stay

No the area near the bus stations is not nice don't stay there. You can stay along the metro line.

The easiest way to get a bus to Valparaiso is to go to the bust station Pajaritos which is also on the main metro subway line Number 1 in the west part of the city, three stops from the end of the line. This means, as per willemspie, anywhere near this Metro line will be convenient.

Which gives options anywhere from a hostel in Barrio Brasil to a hotel in Providencia or las condes.

Thanks for the info, it's very helpful. We are an older couple (65 & 70). Which area is the closest to the Metro line that we want? Any recommendations? Thanks.

The closest place to the bus stations would be near Republica.

Don't think that answers the question. Republica is not a great area either.
There are of course hundreds of options.
For example, B & B in a quiet residential area still only a block from Av Providencia and 5 min walk from Metro is Casa Condell at approx. 50 usd per night. Still lots of good restaurants near and bellavista a 10 min walk or 3 minute taxi fare.
Or in the middle of commercial Providencia area a small but nice hotel the park Plaza on Ricardo Lyon only minutes walk from Los Leones metro is about 135 usd per night.
Once you are on the metro it is a short ride to Pajaritos, maybe 20 minutes or so but very busy in rush hour and not recommended with anything bigger than a daypack.

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