The cheapest fares are with 'Advance' tickets which, as their name implies, need to be booked ahead (preferably by several weeks). They are often only available on off-peak services.
The ('walk up') 'Anytime' single fare is £140.50, with a return costing double that. (£281.00)
The equivalent 'Off Peak' single far is only slightly to cheaper, at £138.80, but you can buy a return for only £1 more (i.e. £139.80).
'Advance' tickets are only sold as singles. Such a ticket for this coming Monday will cost you £132.50 but booking further ahead will significantly reduce the price (e.g. £58.00 is offered on Wed 02/05).
Further reductions are sometimes available by splitting the journey. e.g. on Wed 02/05 you can get from Plymouth to London for £18, and then from London to Manchester for £25, making £43 (plus a bus or tube fare across London) in total.
On the same date you could also travel via Birmingham (with two separate tickets), for £28.00 + £14.50 = £42.50.
Anyway, using sites like Red Spotted Hanky or Trainline is simply madness. Such sites often charge booking fees, and they can't offer fares any cheaper than those shown on the Nation Rail website:
http://www.nationalrail.co.uk/
With the closure of Plymouth City Airport (and the loss of Air Southwest's route to Manchester), there is currently very little competition for the railways. Even so, rail companies still struggle to make profits, as much of what people pay in their fares goes to Network Rail's programme to replace an ageing infrastructure (as the Government cuts back on subsidies).
Chris