A reduction from over 6MB to under 2MB is very good. Your readers will appreciate it. They might not know (or care) about the size difference but they'll be pleased that they can download it quickly. A happy reader is more likely to come back for the next issue.
Using a separate tool to compress a PDF can be useful but sometimes they only reduce the DPI of the images which is what Scribus lets you do anyway. But if it's free then why not give it a try. (OSX Users: You can use Preview to try and reduce the size of a PDF. Open the PDF in Preview, go to menu "File -> Export", open the Quartz Filter drop-down and select "Reduce File Size".)
IMPORTANT NOTE: For anyone thinking about using a free online PDF compressor/reducer: Make sure you read the terms and conditions very carefully. Make sure that (a) you retain copyright of both the original and compressed documents, and (b) the site will not retain a copy of either document. Some of these sites may take liberties with what you send them so be careful. If you have any doubts, don't send them anything.
Generally, "PDF Export -> Color -> Output Intended For : Printer" should only be used if you are printing - or getting something printed - on a machine that needs/prefers CMYK separation. "Output Intended For : Screen/Web" should normally be used if you're not getting something professionally printed, but most print shops will be fine with it anyway. Either way, it's best to check with your manual or print shop to see what's best. Anything you're digitally distributing for a general readership will probably be fine with "Screen/Web".
Setting a maximum image resolution to 72DPI will be, for most purposes, just fine. However, 144DPI might be preferable if you think a lot of your readers may be using large/hi-res displays, or if you think they'll be zooming into what's on the page (e.g. for detailed maps or images that warrant a bit of extra investigation). You can always control this on an image-by-image basis yourself by using GIMP (or a similar package) to resize the image manually before importing into Scribus. This can be a bit tricky at first however so making Scribus do it for you at a document level is easier.
When you have to use an image with transparency it might be worth thinking about how much of the image you want to see. For instance, the "steam + escape rocket" actually only covers a small area of the top-middle of the page. Cropping it in GIMP to be just the bit you need - and then moving the image frame as necessary - might further reduce file size. Similarly, the tip of the escape rocket only covers a tiny bit of the "F" so the actual image needed there should be very small. It's worth mentioning that this sort of optimisation should only really be done once the design has been finalised.
On top of this, there's another option. Once you have the cover design finalised:
* Save the cover page to a new file (so you have a copy to go back to if needed);
* Open the new file and export the page as an image (as JPG, you don't need a transparency);
* Go back to the original document;
* Remove everything from the cover page (remember that you have a backup);
* Add an image frame to cover the whole page;
* Import the image exported from the cover page document.
This way you only have one image on the page which covers the same physical area but will be smaller in size than all the original images combined. If you need to change the cover then open the cover page document, make the changes, then re-export and Scribus will pick-up the change automatically (as long as you use the same export file name). It's a bit more work but it might make a big difference on covers that have a lot of "overlaps". The downside of this is that the text becomes rasterised so will not scale up as nicely as it would otherwise do. You've just got to decide what is best for you (you might be able to keep some of the text in Scribus, it depends on the design).
Anyway, I'll be interested in hearing about how you get on with my hanging quotes suggestion. There's a chance that you could come up with a much better idea while you are experimenting.