There are some feeds that often contain large numbers of updated items. You can use Apple-/ to skip through unread items, and Apple-K to "Mark All As Read", but there's no keyboard shortcut to mark all the items in a feed as read and proceed to the next unread item. That's what this Applescript does:
tell application "System Events"
tell process "NetNewsWire"
set frontmost to true
tell menu bar 1
tell menu bar item "News"
tell menu 1
click menu item "Mark All as Read"
click menu item "Go to Next Unread"
end tell
end tell
end tell
end tell
end tell
Save the script in ~/Library/Scripts/NetNewsWire, then assign it to a keyboard shortcut (eg Apple-;) using a Quicksilver trigger (you can't give random scripts keyboard shortcuts using the Keyboard preference pane, and if you run it from NetNewsWire's scripts menu it locks up). You'll have to have GUI scripting enabled as well (use Applescript Utility for that).
Update... alternatively you could just press 'L' :-/