Of course. Look at the San Francisco to Vancouver (return) example:
Regular: SFO - YVR: $385 Tripdelta: Oakland - Bellingham (two tickets): $164
You save $221 by picking two airports that are, by locals, considered good airports (I live in Vancouver, we all use Bellingham!)
The great thing is: Even when you're not a local, you just enter Vancouver, and we know about it!