The "best" route depends upon how flat you need. The flattest option would probably be following the Grand Union to Slough, down to Eton then following the Thames to Oxford.
Alternatively, through Uxbridge and Wexham to Slough (avoid the A412), then A4 through Maidenhead to pick up the Henley Road just before the A404. Then A4130 through Henley to Wallingford and A4155 from Wallingford to Oxford.
A bit further but missing out the lumps around Temple and Aston would be to stick with the A4 to Hare Hatch, north on the A321 through Wargrave to Henley, A4130 to Wallingford and A4074 to Oxford.
A bit further but possibly flatter still would be to stick on the A4 through to Sonning, then cross the river at Sonning Eye and head SW on the A4155 for a bit to Caversham. Then you could follow the A4074 all the way from Caversham to Oxford.
For a flat route, you'd be going a lot further through Reading and out on the A329 to Pangbourne, Streatley etc) as there are a lot of hills round Henley, Nettlebed etc.
I don't think you could call anything north of that particularly flat, as you are hitting the middle of the Chilterns round Wycombe or Amersham, and they can be ruddy lumpy.