If your earning is related to work you'll probably have to go with the hub carrier, especially if you're under directives or being scrutinized (e.g. an employee for a company). Airfares will usually be the same across the board, and if you take a connecting flight out of FF loyalty you could see a slightly higher fare (from more taxes) and be criticized for not spending time efficiently (even if it's not counted as work time, but especially if it is). I didn't know anyone at work who was earning work-related miles primarily in any airline other than DL (from ATL), even though that may have had accounts with other carriers.

If your earning is from leisure or more discretionary than it can get more interesting. Sometimes other carriers will do spot specials out of competitors' hubs just to get at the hub carrier over something, and if you can combine that with FF benefits it can work out well. My main earning is on NW, for example, and they have done some deals to jab at DL that I've been able to take advantage of (despite both airlines being in Skyteam). NW also has the better upgrade policy.